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MEpedia:Non-cytolytic enterovirus

2021-01-12T21:11:34Z

Fireballsky:Fireballsky moved page MEpedia:Non-cytolytic enterovirus to Corticosteroids given during acute viral infection may trigger myalgic encephalomyelitis over redirect: revert

#REDIRECT [[Corticosteroids given during acute viral infection may trigger myalgic encephalomyelitis]]

Corticosteroids given during acute viral infection may trigger myalgic encephalomyelitis

2021-01-12T21:11:31Z

Fireballsky:Fireballsky moved page MEpedia:Non-cytolytic enterovirus to Corticosteroids given during acute viral infection may trigger myalgic encephalomyelitis over redirect: revert

{{Cleanup|reason=The page title is a complete sentence, not a topic. consider moving page content to a page on "corticosteroids", instead of having a separate page. (if kept as a separate page, it would need a category.)|date=22 December 2019}}

==Acute viral infection plus corticosteroids may cause ME/CFS ==
[[John Chia|Dr John Chia]] has observed that corticosteroids inadvertently prescribed during an acute viral infection substantially increase the risk of developing myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) from that infection. Via his meticulous investigations into patients' medical histories, Dr Chia discovered that hundreds of his ME/CFS patients were given corticosteroids precisely during the time that they came down with a flu-like illness, gastrointestinal upset or other viral infection.<ref>{{Cite web|url=http://www.investinme.org/IIMEC5.shtml|title=Dr John Chia: Enterovirus Infection in ME/CFS. Presentation at the Invest in ME International ME Conference, London 2010 (available on DVD). Timecodes: 07:31 and 28:00.|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|quote=VIDEO TIMECODE 07:31 — If the patient already had chickenpox before and they then develop flu-like illness with chickenpox-like rashes that's enterovirus until proven otherwise. But the rash could look like measles, German measles, it could look like hives. So very often people travel, eat some shellfish, and develop this hives, all over. Went to the emergency room, the emergency room doctor will say, 'Oh well, you ate lobster, you must be allergic to shellfish.' So what's the next thing they get? They get some prednisone, steroids, and that disease never ended. They develop chronic fatigue syndrome after that. We hear this hundreds of times. VIDEO TIMECODE 28:00 — Glucocorticoids: if the patient developed a viral infection, and with symptoms suggestive of asthma, they are often given steroids, because it's the mainstay of therapy. That can shift the immune response to Th2, not to mention you'll drop the T-lymphocytes down to practically zero.}}</ref> Thus there appears to be a causal equation of:

'''Acute infection + corticosteroids = ME/CFS'''

Dr Chia says one reason corticosteroids can be inadvertently prescribed during an acute enteroviral infection is because an [[enterovirus]] rash can look like [[Urticaria|hives]], so if a doctor questions what the patient ate, and they happened to eat shellfish recently, the doctor may incorrectly assume the rash is a hives rash, resulting from allergy to shellfish. So the doctor may then put the patient on a course of corticosteroids such as prednisone, as this is the normal treatment for hives.

Thus the patient has an acute enterovirus infection, and needs a strong immune response to fight this infection, yet receives immunosuppressing corticosteroids, because the viral rash was misdiagnosed as hives.

Similarly, if a patient comes down with an acute viral infection and its symptoms are suggestive of asthma, they may also be inappropriately prescribed corticosteroids, because that is how [[asthma]] is treated.

== Immunosuppression by corticosteroids and chronic stress ==
Corticosteroids suppress the Th1 antiviral/intracellular immune response,<ref>{{Cite journal|last=Elenkov|first=Ilia J.|date=Jun 2004|title=Glucocorticoids and the Th1/Th2 balance|url=https://www.ncbi.nlm.nih.gov/pubmed/15265778|journal=Annals of the New York Academy of Sciences|volume=1024|pages=138–146|doi=10.1196/annals.1321.010|issn=0077-8923|pmid=15265778}}</ref> and suppresses T-cell function.<ref>{{Cite journal|last=Davis|first=Trevor E|last2=Kis-Toth|first2=Katalin|last3=Szanto|first3=Attila|last4=Tsokos|first4=George C.|date=Jul 2013|title=Glucocorticoids suppress T cell function by upregulating microRNA 98|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713788/|journal=Arthritis and rheumatism|volume=65|issue=7|pages=1882–1890|doi=10.1002/art.37966|issn=0004-3591|pmc=3713788|pmid=23575983}}</ref>

Interestingly, ME/CFS is usually precipitated by viral infection, and several studies found it is common to experience major psychological chronic stress in the year prior to developing ME/CFS.<ref>{{Cite journal|last=Hatcher|first=Simon|last2=House|first2=Allan|date=Oct 2003|title=Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study|url=https://www.ncbi.nlm.nih.gov/pubmed/14580073|journal=Psychological Medicine|volume=33|issue=7|pages=1185–1192|doi=10.1017/s0033291703008274|issn=0033-2917|pmid=14580073}}</ref><ref>{{Cite journal|last=Theorell|first=T.|last2=Blomkvist|first2=V.|last3=Lindh|first3=G.|last4=Evengård|first4=B.|date=May 1999|title=Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a nonspecific life crisis|url=https://www.ncbi.nlm.nih.gov/pubmed/10367610|journal=Psychosomatic Medicine|volume=61|issue=3|pages=304–310|issn=0033-3174|pmid=10367610}}</ref><ref>{{Cite journal|last=Salit|first=Irving E.|date=1997-01-01|title=Precipitating factors for the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S0022395696000507|journal=Journal of Psychiatric Research|volume=31|issue=1|pages=59–65|doi=10.1016/S0022-3956(96)00050-7|issn=0022-3956}}</ref> Chronic psychological stress elevates cortisol which suppresses the Th1 antiviral/intracellular immune response,<ref>{{Cite journal|last=Dhabhar|first=Firdaus S|date=2008-03-15|title=Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection versus Immunopathology|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869337/|journal=Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology|volume=4|issue=1|pages=2–11|doi=10.1186/1710-1492-4-1-2|issn=1710-1484|pmc=2869337|pmid=20525121}}</ref> and the T-cell response.<ref>{{Cite journal|last=Dhabhar|first=Firdaus S|date=2008-03-15|title=Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection versus Immunopathology|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869337/|journal=Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology|volume=4|issue=1|pages=2–11|doi=10.1186/1710-1492-4-1-2|issn=1710-1484|pmc=2869337|pmid=20525121}}</ref> Thus immonologically, chronic stress has a similar effect to corticosteroid administration, and both these factors appear to increase the risk of development of ME/CFS from viral infection.

== See also ==
* [[Enterovirus]]
* [[Stress]]
* [[John Chia]]

== References ==
<references />

Autoantibody

2020-12-26T23:56:26Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|Mu-opioid receptor
|15% (9 of 60), 0 of 30 controls<ref name=":3" />
|
|
|-
|Dopamine receptor D2
|5% (3 of 60), 0 of 30 controls<ref name=":3" />
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60), 0 of 30 controls<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|'''Neurotransmitters'''
|
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

61.5% (72 of 117) ME/CFS, 14% (6 of 43) "chronic fatigue", 6% (2 of 35) controls<ref>{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=https://pubmed.ncbi.nlm.nih.gov/23664637/|journal=Journal of Affective Disorders|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|52% (31 of 60) nuclear envelope antigens, mostly Lamin B1<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|52% (31 of 60) nuclear envelope antigens, some cytoplasmic proteins<ref name=":11" />
|
|
|-
|'''Cytoplasmic membrane antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=Dec 2007|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />

68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>

<ref name=":12">{{Cite journal|last=Hilgers|first=A.|last2=Frank|first2=J.|date=1994|title=[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes]|url=https://pubmed.ncbi.nlm.nih.gov/7856214/|journal=Wiener Medizinische Wochenschrift (1946)|volume=144|issue=16|pages=399–406|issn=0043-5341|pmid=7856214}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=Oct 2006|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=Dec 2012|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=Jun 2008|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=Apr 2011|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|TPO
|<ref name=":12" />
|
|
|-
|
|
|
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=Jul 2001|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Single nucleotide polymorphism

2020-12-26T02:23:18Z

Fireballsky:/* Learn more */

{{stub}}
A '''single nucleotide polymorphism''' (SNP) is a potential genetic mutation that occurs in a single spot in the human genome.<ref>{{Cite web|url=https://ghr.nlm.nih.gov/primer/genomicresearch/snp|title=What are single nucleotide polymorphisms (SNPs)?|last=Genetics Home Reference|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Genetics Home Reference|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-10-03}}</ref> A single spot in the human genome is represented physically by a particular nucleotide base-pair in the DNA, such as cytosine-guanine or adenine-thymine. For example, 60% of the general population may have a cytosine-guanine base pair at a particular location in their DNA, but 40% of the population may have a adenine-thymine base pair at that location instead. SNP's are often represented by an "rs" number, such as "rs53576".<ref>{{Cite web|url=https://www.snpedia.com/index.php/Rs53576|title=rs53576 - SNPedia|website=www.snpedia.com|access-date=2019-10-06}}</ref>

== Autoimmune ==
A 2020 study found two autoimmune-related SNPs associated with ME/CFS patients with an infectious onset.<ref>{{Cite journal|last=Steiner|first=Sophie|last2=Becker|first2=Sonya C.|last3=Hartwig|first3=Jelka|last4=Sotzny|first4=Franziska|last5=Lorenz|first5=Sebastian|last6=Bauer|first6=Sandra|last7=Löbel|first7=Madlen|last8=Stittrich|first8=Anna B.|last9=Grabowski|first9=Patricia|date=2020|title=Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset|url=https://www.frontiersin.org/articles/10.3389/fimmu.2020.00578/full|journal=Frontiers in Immunology|language=English|volume=11|doi=10.3389/fimmu.2020.00578|issn=1664-3224}}</ref>

'''PTPN22 rs2476601''' aka R620W or C1858T (OR 1.63, CI 1.04–2.55, p = 0.016) - ''PTPNN22 (Tyrosine phosphatase non-receptor type 22)''

'''CTLA4 rs3087243''' (OR 1.53, CI 1.17–2.03, p = 0.001) - ''CTLA4 (Cytotoxic T-lymphocyte-associated protein 4)''

PTPN22 rs2476601 has been found in multiple autoimmune diseases including Hashimoto's thyroiditis, psoriasis, and Type I diabetes.<ref>{{Cite journal|last=Lee|first=Hye-Soon|last2=Kang|first2=Jungoo|last3=Yang|first3=Seiwon|last4=Kim|first4=Dukhee|last5=Park|first5=Yongsoo|date=2011-11|title=Susceptibility influence of a PTPN22 haplotype with thyroid autoimmunity in Koreans|url=https://pubmed.ncbi.nlm.nih.gov/22069277/|journal=Diabetes/Metabolism Research and Reviews|volume=27|issue=8|pages=878–882|doi=10.1002/dmrr.1265|issn=1520-7560|pmid=22069277}}</ref><ref>{{Cite journal|last=Chen|first=Yu-Fu|last2=Chang|first2=Jeffrey S.|date=2012-08|title=PTPN22 C1858T and the risk of psoriasis: a meta-analysis|url=https://pubmed.ncbi.nlm.nih.gov/22544573/|journal=Molecular Biology Reports|volume=39|issue=8|pages=7861–7870|doi=10.1007/s11033-012-1630-z|issn=1573-4978|pmid=22544573}}</ref><ref>{{Cite journal|last=Steck|first=AK|last2=Baschal|first2=EE|last3=Jasinski|first3=JM|last4=Boehm|first4=BO|last5=Bottini|first5=N|last6=Concannon|first6=P|last7=Julier|first7=C|last8=Morahan|first8=G|last9=Noble|first9=JA|date=2009-12|title=rs2476601 T allele (R620W) defines high-risk PTPN22 type I diabetes-associated haplotypes with preliminary evidence for an additional protective haplotype|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805459/|journal=Genes and immunity|volume=10|issue=Suppl 1|pages=S21–S26|doi=10.1038/gene.2009.87|issn=1466-4879|pmc=2805459|pmid=19956096}}</ref>

== Learn more ==
* [https://www.snpedia.com/index.php/Glossary SNPedia's glossary]
* [https://learngendev.azurewebsites.net/content/precision/snips/ Genetic Science Learning Center]

==References ==
{{reflist}}

[[Category:Biochemistry and cell biology]]

Autoantibody

2020-11-27T20:41:41Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

61.5% (72 of 117) ME/CFS, 14% (6 of 43) "chronic fatigue", 6% (2 of 35) controls<ref>{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=https://pubmed.ncbi.nlm.nih.gov/23664637/|journal=Journal of Affective Disorders|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|52% (31 of 60) nuclear envelope antigens, mostly Lamin B1<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|52% (31 of 60) nuclear envelope antigens, some cytoplasmic proteins<ref name=":11" />
|
|
|-
|'''Cytoplasmic membrane antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />

68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>

<ref name=":12">{{Cite journal|last=Hilgers|first=A.|last2=Frank|first2=J.|date=1994|title=[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes]|url=https://pubmed.ncbi.nlm.nih.gov/7856214/|journal=Wiener Medizinische Wochenschrift (1946)|volume=144|issue=16|pages=399–406|issn=0043-5341|pmid=7856214}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|TPO
|<ref name=":12" />
|
|
|-
|
|
|
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-26T00:17:50Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|52% (31 of 60) nuclear envelope antigens, mostly Lamin B1<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|52% (31 of 60) nuclear envelope antigens, some cytoplasmic proteins<ref name=":11" />
|
|
|-
|'''Cytoplasmic membrane antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />

68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>

<ref name=":12">{{Cite journal|last=Hilgers|first=A.|last2=Frank|first2=J.|date=1994|title=[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes]|url=https://pubmed.ncbi.nlm.nih.gov/7856214/|journal=Wiener Medizinische Wochenschrift (1946)|volume=144|issue=16|pages=399–406|issn=0043-5341|pmid=7856214}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|TPO
|<ref name=":12" />
|
|
|-
|
|
|
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Hashimoto's thyroiditis (hypothyroidism)

2020-11-25T20:48:43Z

Fireballsky:/* HLA risk alleles */

[[File:MECFS comorbid autoimmune.jpg|alt=Hashimoto's thyroiditis & ME/CFS|thumb|Hashimoto's thyroiditis found in 17-20% of ME/CFS patients<ref>{{Cite journal|date=2018-06-01|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease|url=https://www.sciencedirect.com/science/article/pii/S1568997218300880|journal=Autoimmunity Reviews|language=en|volume=17|issue=6|pages=601–609|doi=10.1016/j.autrev.2018.01.009|issn=1568-9972}}</ref>
Source: Sotzny et al (2018), [[EUROMENE]] project.
]]'''Hashimoto's thyroiditis''' or '''Hashimoto's disease''' (also known as '''chronic lymphocytic thyroiditis''') is an [[autoimmune disease]] affecting [[thyroid]] function, where the body's [[immune system]] creates antibodies that attack and inflame the thyroid.

Hashimoto's thyroiditis is the most common cause of '''hypothyroidism''' (or underactive thyroid or low thyroid) in the United States. Hypothyroidism is an [[endocrine]] disorder in which the [[thyroid gland]] does not produce enough [[thyroid hormone]] called T4 (thyroxine), which is used to help the body use energy as well help maintain function of the brain, heart, muscle, and other organs.<ref name=":3">{{Cite web|url=https://www.thyroid.org/hashimotos-thyroiditis/|title=Hashimoto’s Thyroiditis|website=American Thyroid Association|language=en-US|access-date=2020-08-26}}</ref><ref>{{Cite web|url=https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism|title=Hypothyroidism (Underactive Thyroid) {{!}} NIDDK|website=National Institute of Diabetes and Digestive and Kidney Diseases|language=en-US|access-date=2020-08-26}}</ref>

Hashimoto's thyroiditis is found in an estimated 17% - 20% of ME/CFS patients.<ref>{{Cite journal|date=2018-06-01|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease|url=https://www.sciencedirect.com/science/article/pii/S1568997218300880|journal=Autoimmunity Reviews|language=en|volume=17|issue=6|pages=601–609|doi=10.1016/j.autrev.2018.01.009|issn=1568-9972}}</ref><ref>{{Cite journal|last=Castro-Marrero|first=Jesús|last2=Faro|first2=Mónica|last3=Aliste|first3=Luisa|last4=Sáez-Francàs|first4=Naia|last5=Calvo|first5=Natalia|last6=Martínez-Martínez|first6=Alba|last7=de Sevilla|first7=Tomás Fernández|last8=Alegre|first8=Jose|date=Sep 2017|title=Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study|url=https://pubmed.ncbi.nlm.nih.gov/28596045/|journal=Psychosomatics|volume=58|issue=5|pages=533–543|doi=10.1016/j.psym.2017.04.010|issn=1545-7206|pmid=28596045}}</ref>

A 2001 Swedish study of 219 chronic fatigue patients (90% women), used fine-needle aspiration (FNA) cytology to test thyroid function. 87 of 219 (40%) were diagnosed with cytological lymphocytic thyroiditis.<ref>{{Cite journal|last=Wikland|first=B.|last2=Löwhagen|first2=T.|last3=Sandberg|first3=P. O.|date=2001-03-24|title=Fine-needle aspiration cytology of the thyroid in chronic fatigue|url=https://pubmed.ncbi.nlm.nih.gov/11289370/|journal=Lancet (London, England)|volume=357|issue=9260|pages=956–957|doi=10.1016/s0140-6736(05)71654-8|issn=0140-6736|pmid=11289370}}</ref>
==Signs and symptoms==
Symptoms of an underactive thyroid (hypothyroidism) due to Hashimoto's include:
* [[Weight gain]]
* [[Hair loss]] (or thinning)
* [[Fatigue]]
* [[Body temperature|Sensitivity to cold]]
* Constipation
* [[arthralgia|Joint pain]] and [[myalgia|muscle pain]]
* Excessive or prolonged menstrual bleeding
* [[Depression]]

== Causes ==
There are many risk factors and potential causes for thyroid disease. Hashimoto's is the number one cause of hypothyroidism in the United States.<ref name=":3" />

=== Hashimoto's ===
The exact cause of Hashimoto's thyroiditis is unknown. Many researchers and physicians believe genetics and/or a virus could play a role in the development of this autoimmune disease.<ref>{{Cite web|url=https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease|title=Hashimoto's Disease {{!}} NIDDK|website=National Institute of Diabetes and Digestive and Kidney Diseases|language=en-US|access-date=2020-10-21}}</ref>

=== Hypothyroidism ===
* [[Hashimoto's thyroiditis]], also known as Hashimoto's disease
* Congenital hypothyroidism, which is when a person is born with hypothyroidism
* Thyroid surgery that removes all or part of the thyroid
* Past radiation treatment of the thyroid
* Other causes include certain medicines, too much or too little [[iodine]] in the diet, or pituitary disease (which is another endocrine disease).<ref>{{Cite web|url=https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism|title=Hypothyroidism (Underactive Thyroid) {{!}} NIDDK|website=National Institute of Diabetes and Digestive and Kidney Diseases|language=en-US|access-date=2020-10-21}}</ref>

== Cellular hypothyroidism ==
Some patients may exhibit Hashimoto's hypothyroid symptoms, yet display normal ranges in their thyroid blood tests. This could be an indication of “''cellular or peripheral hypothyroidism''”, where there's a deficiency at the cellular level. While thyroid hormone production may be functioning properly, the transportation of thyroid hormone into cells will be hindered if there is mitochondrial dysfunction.<ref>{{Cite journal|last=Kelly|first=Tammas|date=Dec 2016|title=A hypothesis on the mechanism of action of high-dose thyroid in refractory mood disorders|url=https://pubmed.ncbi.nlm.nih.gov/27876122/|journal=Medical Hypotheses|volume=97|pages=16–21|doi=10.1016/j.mehy.2016.09.022|issn=1532-2777|pmid=27876122}}</ref>

[[Mitochondria dysfunction|Mitochondrial dysfunction]] has been implicated countless times, not only as a contributor to, but often cited as the immediate cause of ME/CFS symptoms.<ref>{{Cite journal|last=Myhill|first=Sarah|last2=Booth|first2=Norman E.|last3=McLaren-Howard|first3=John|date=2009-01-15|title=Chronic fatigue syndrome and mitochondrial dysfunction|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/|journal=International Journal of Clinical and Experimental Medicine|volume=2|issue=1|pages=1–16|issn=1940-5901|pmc=2680051|pmid=19436827}}</ref><ref>{{Cite journal|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|date=2019-03-01|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398432/|journal=PeerJ|volume=7|doi=10.7717/peerj.6500|issn=2167-8359|pmc=6398432|pmid=30847260}}</ref><ref>{{Cite journal|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|date=2019-02-27|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|url=https://www.nature.com/articles/s41598-019-39060-1|journal=Scientific Reports|language=en|volume=9|issue=1|pages=2914|doi=10.1038/s41598-019-39060-1|issn=2045-2322}}</ref>

== Viral triggers ==
[[Virus]]es are common triggers of Hashimoto's thyroiditis, and hypothyroidism. [[Epstein-Barr virus|Epstein-Barr virus (EBV)]] and [[Human herpesvirus 6|Human Herpesvirus 6 (HHV-6)]] are perhaps two of the most common viral triggers for Hashimoto. Others include [[Herpes simplex virus|Herpes Simplex 1 and 2 (HSV)]], [[Cytomegalovirus|Cytomegalovirus (CMV)]], [[Enterovirus]], and [[Parvovirus B19]].

===Studies linking viral infections to Hashimoto's & ME/CFS===
Studies suggesting a viral trigger for Hashimoto's thyroiditis and autoimmune thyroiditis (AIT) that are also viruses commonly associated with ME/CFS.
{| class="wikitable"
|'''Epstein-Barr virus serology in patients with autoimmune thyroiditis'''
J Vrbikova, I Janatkova, V Zamrazil, F Tomiska, T Fucikova<ref>{{Cite journal|last=Vrbikova|first=J.|last2=Janatkova|first2=I.|last3=Zamrazil|first3=V.|last4=Tomiska|first4=F.|last5=Fucikova|first5=T.|date=1996|title=Epstein-Barr virus serology in patients with autoimmune thyroiditis|url=https://pubmed.ncbi.nlm.nih.gov/8750577/|journal=Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association|volume=104|issue=1|pages=89–92|doi=10.1055/s-0029-1211428|issn=0947-7349|pmid=8750577}}</ref>
|1996
|Endocrinology study shows significantly higher presence of active Epstein-Barr virus (EBV) in those with autoimmune thyroiditis compared to healthy controls.

7 of 22 (32%) patients were positive for EBV early antigen (EA-D) antibodies, versus 2 of 35 (6%) controls.
|-
|'''Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis'''

Elisabetta Caselli, Maria Chiara Zatelli, Roberta Rizzo, Sabrina Benedetti, Debora Martorelli, Giorgio Trasforini, Enzo Cassai, Ettore C. degli Uberti, Dario Di Luca, Riccardo Dolcetti<ref name=":1">{{Cite journal|last=Caselli|first=Elisabetta|last2=Zatelli|first2=Maria Chiara|last3=Rizzo|first3=Roberta|last4=Benedetti|first4=Sabrina|last5=Martorelli|first5=Debora|last6=Trasforini|first6=Giorgio|last7=Cassai|first7=Enzo|last8=degli Uberti|first8=Ettore C.|last9=Di Luca|first9=Dario|date=2012-10-04|title=Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464215/|journal=PLoS Pathogens|volume=8|issue=10|doi=10.1371/journal.ppat.1002951|issn=1553-7366|pmc=3464215|pmid=23055929}}</ref>
|2012
|Study using fine needle aspirates (FNA) thyroid biopsies found HHV-6 DNA in 28 of 34 (82%) Hashimoto's thyroiditis patients and 3 of 28 (10%) controls.
|-
|'''Inflammation and Increased Myxovirus Resistance Protein A Expression in Thyroid Tissue in the Early Stages of Hashimoto's Thyroiditis'''
Sara Salehi Hammerstad, Frode Lars Jahnsen, Sisko Tauriainen, Heikki Hyöty, Trond Paulsen, Ingrid Norheim, and Knut Dahl-Jørgensen<ref>{{Cite journal|last=Hammerstad|first=Sara Salehi|last2=Jahnsen|first2=Frode Lars|last3=Tauriainen|first3=Sisko|last4=Hyöty|first4=Heikki|last5=Paulsen|first5=Trond|last6=Norheim|first6=Ingrid|last7=Dahl-Jørgensen|first7=Knut|date=Mar 2013|title=Inflammation and Increased Myxovirus Resistance Protein A Expression in Thyroid Tissue in the Early Stages of Hashimoto's Thyroiditis|url=https://www.liebertpub.com/doi/full/10.1089/thy.2012.0264|journal=Thyroid|volume=23|issue=3|pages=334–341|doi=10.1089/thy.2012.0264|issn=1050-7256}}</ref>
|2013
|Study found Enterovirus RNA in 11% of Hashimoto's thyroiditis (HT) patients, versus 0% of controls.
|-
|'''The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases'''
Andrea Janegova, Pavol Janega, Boris Rychly, Kristina Kuracinova, Pavel Babal<ref>{{Cite journal|last=Janegova|first=Andrea|last2=Janega|first2=Pavol|last3=Rychly|first3=Boris|last4=Kuracinova|first4=Kristina|last5=Babal|first5=Pavel|date=2015|title=The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases|url=https://pubmed.ncbi.nlm.nih.gov/25931043/|journal=Endokrynologia Polska|volume=66|issue=2|pages=132–136|doi=10.5603/EP.2015.0020|issn=2299-8306|pmid=25931043}}</ref>
|2015
|Graves' and Hashimoto's disease specimens were used in this study, finding a high prevalence of EBV infection. ''"We assume that high prevalence of EBV infection in cases of Hashimoto's and Graves' diseases imply a potential aetiological role of EBV in autoimmune thyroiditis"''
|-
|'''Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases'''
A Sultanova, M Cistjakovs, S Gravelsina, S Chapenko, S Roga, E Cunskis, [[Zaiga Nora-Krukle|Z Nora-Krukle]], V Groma, I Ventina, [[Modra Murovska|M Murovska]]<ref name=":2">{{Cite journal|last=Sultanova|first=A.|last2=Cistjakovs|first2=M.|last3=Gravelsina|first3=S.|last4=Chapenko|first4=S.|last5=Roga|first5=S.|last6=Cunskis|first6=E.|last7=Nora-Krukle|first7=Z.|authorlink7=Zaiga Nora-Krukle|last8=Groma|first8=V.|last9=Ventina|first9=I.|last10=Murovska|first10=M.|authorlink10=Modra Murovska|date=Jan 2017|title=Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases|url=https://pubmed.ncbi.nlm.nih.gov/27693656/|journal=Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases|volume=23|issue=1|pages=50.e1–50.e5|doi=10.1016/j.cmi.2016.09.023|issn=1469-0691|pmid=27693656}}</ref>
|2017
|A study comparing the involvement of HHV-6 infection between autoimmune thyroiditis (AIT) patients and healthy controls. Thyroid gland biopsies confirmed active persistent HHV-6 infection in 18 of 44 (41%) AIT patients and 1 of 17 (6%) healthy controls.
|-
|'''Human herpesvirus 6A active infection in patients with autoimmune Hashimoto's thyroiditis'''
Noorossadat Seyyedi, Gholamreza Rafiei Dehbidi, Mozhgan Karimi, Amir Asgari, Babak Esmaeili, Farahnaz Zare, Ali Farhadi, Mohammad Hossein Dabbaghmanesh, Forough Saki, Abbas Behzad-Behbahani<ref>{{Cite journal|last=Seyyedi|first=Noorossadat|last2=Dehbidi|first2=Gholamreza Rafiei|last3=Karimi|first3=Mozhgan|last4=Asgari|first4=Amir|last5=Esmaeili|first5=Babak|last6=Zare|first6=Farahnaz|last7=Farhadi|first7=Ali|last8=Dabbaghmanesh|first8=Mohammad Hossein|last9=Saki|first9=Forough|date=Nov 2019|title=Human herpesvirus 6A active infection in patients with autoimmune Hashimoto's thyroiditis|url=https://pubmed.ncbi.nlm.nih.gov/31751524/|journal=The Brazilian Journal of Infectious Diseases: An Official Publication of the Brazilian Society of Infectious Diseases|volume=23|issue=6|pages=435–440|doi=10.1016/j.bjid.2019.10.004|issn=1678-4391|pmid=31751524}}</ref>
|2019
|In this study, 38% of patients with Hashimoto’s disease had active HHV-6A infections.
|-
|'''Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto’s thyroiditis: A case-control study'''
Samir Naeim Assaad, Marwa Ahmed Meheissen, Eman Tayae Elsayed, Saher N. Alnakhal, Tarek M. Salema<ref name=":0">{{Cite journal|last=Assaad|first=Samir Naeim|last2=Meheissen|first2=Marwa Ahmed|last3=Elsayed|first3=Eman Tayae|last4=Alnakhal|first4=Saher N.|last5=Salem|first5=Tarek M.|date=2020-03-12|title=Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto’s thyroiditis: A case-control study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090364/|journal=Journal of Clinical & Translational Endocrinology|volume=20|doi=10.1016/j.jcte.2020.100222|issn=2214-6237|pmc=7090364|pmid=32215255}}</ref>
|2020
|This study included 60 Hashimoto's thyroiditis patients and 60 healthy controls. Epstein-Barr virus (EBV) Early Antigen (EA) was positive in 20 of 60 (33%) HT patients and 4 of 60 (7%) healthy controls, indicating a higher prevalence of active EBV in Hashimoto patients.
|-
|'''HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis'''

Alina Sultanova, Maksims Cistjakovs, Liba Sokolovska, Katerina Todorova, Egils Cunskis, Modra Murovska<ref>{{Cite journal|last=Sultanova|first=Alina|last2=Cistjakovs|first2=Maksims|last3=Sokolovska|first3=Liba|last4=Todorova|first4=Katerina|last5=Cunskis|first5=Egils|last6=Murovska|first6=Modra|date=Jun 26, 2020|title=HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis|url=https://pubmed.ncbi.nlm.nih.gov/32604892/|journal=Viruses|volume=12|issue=6|doi=10.3390/v12060689|issn=1999-4915|pmc=7354462|pmid=32604892}}</ref>
|2020
|Markers of active HHV-6 infection were predominantly found in patients with autoimmune thyroiditis (AIT). 56% of AIT patients (vs. 6% controls) were found to have active HHV-6 infection in thyroid gland tissue.
|}

== Sleep apnea ==
Hashimoto's thyroiditis (HT) and sleep apnea can both result in extreme fatigue. New evidence suggests a connection between Hashimoto's and obstructive sleep apnea (OSA). In fact, the association could be bi-directional, where either condition could potentially develop as a consequence of the other.<ref>{{Cite journal|last=Xerfan|first=Ellen M.S.|last2=Facina|first2=Anamaria S.|last3=Andersen|first3=Monica L.|last4=Tufik|first4=Sergio|last5=Tomimori|first5=Jane|date=2019-11-15|title=Hashimoto Thyroiditis as a Cause or Consequence of Obstructive Sleep Apnea|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853408/|journal=Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine|volume=15|issue=11|pages=1703|doi=10.5664/jcsm.8054|issn=1550-9389|pmc=6853408|pmid=31739867}}</ref>

==HLA risk alleles==
Variations in several human leukocyte antigen (HLA) complex family of genes have been studied as possible risk factors for Hashimoto thyroiditis. Associations have been found between Hashimoto's disease and the following HLA alleles:<ref>{{Cite web|url=https://selfdecode.com/blog/article/hla-drb1-thyroid-autoimmunity-92/|title=SelfDecode {{!}} Blog|website=selfdecode.com|access-date=2020-08-26}}</ref><ref>{{Cite journal|last=Tashiro|first=Ryosuke|last2=Niizuma|first2=Kuniyasu|last3=Khor|first3=Seik-Soon|last4=Tokunaga|first4=Katsushi|last5=Fujimura|first5=Miki|last6=Sakata|first6=Hiroyuki|last7=Endo|first7=Hidenori|last8=Inoko|first8=Hidetoshi|last9=Ogasawara|first9=Koetsu|date=2019-08-14|title=Identification of HLA-DRB1*04:10 allele as risk allele for Japanese moyamoya disease and its association with autoimmune thyroid disease: A case-control study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220858|journal=PLOS ONE|language=en|volume=14|issue=8|pages=e0220858|doi=10.1371/journal.pone.0220858|issn=1932-6203|pmc=PMC6693760|pmid=31412073}}</ref><ref name=":4">{{Cite journal|last=Lande|first=Asgeir|last2=Fluge|first2=Øystein|last3=Strand|first3=Elin B.|last4=Flåm|first4=Siri T.|last5=Sosa|first5=Daysi D.|last6=Mella|first6=Olav|last7=Egeland|first7=Torstein|last8=Saugstad|first8=Ola D.|last9=Lie|first9=Benedicte A.|date=2020-03-24|title=Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.nature.com/articles/s41598-020-62157-x|journal=Scientific Reports|language=en|volume=10|issue=1|pages=5267|doi=10.1038/s41598-020-62157-x|issn=2045-2322}}</ref>
* C*07:04
* DQB1*03:03
* DRB1
* DRB1*04:10

=== ME/CFS and Hashimoto's ===
In a large 2020 study, CFS patients with [[Human leukocyte antigen genes|Human Leukocyte Antigen]] (HLA) risk alleles ('''C*07:04''' and '''DQB1*03:03''') were found to share the following [[Autoimmune disease|autoimmune diseases]], ordered by frequency:<ref name=":4" />
# [[Hashimoto's thyroiditis]]
# Psoriasis
# [[Rheumatoid arthritis]]
# Alopecia areata
# Crohn’s disease or [[ulcerative colitis]]

==Diagnosis==
Hashimoto's thyroiditis is usually diagnosed based on multiple examinations, often beginning with hypothyroid symptom evaluation. This can be accompanied by blood tests and ultrasound.

Blood tests indicating Hashimoto's disease include elevated levels of thyroperoxidase antibodies (TPO), and elevated levels of thyroid stimulating hormone (TSH). Other lab testing can include Thyroglobulin antibodies (Tg), Free thyroxine (T4), or Free triiodothyronine (T3).

This might be followed by an ultrasound to confirm an enlarged thyroid gland, and other features of Hashimoto's thyroiditis.<ref>{{Cite web|url=https://www.thyroid.org/hashimotos-thyroiditis/|title=Hashimoto’s Thyroiditis|website=American Thyroid Association|language=en-US|access-date=2020-08-26}}</ref>

== Treatments ==

=== Hormone Replacement ===
[[Levothyroxine]] - If you are found to have a thyroid hormone deficiency, resulting in elevated TSH levels, your doctor might prescribe hormone replacement therapy. Levothyroxine is a synthetic thyroid hormone used to normalize TSH and hormone levels, leading to hypothyroid symptom improvement.<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/hashimotos-disease/diagnosis-treatment/drc-20351860|title=Hashimoto's disease - Diagnosis and treatment - Mayo Clinic|website=www.mayoclinic.org|access-date=2020-10-18}}</ref>

=== Target Infection ===
[[Antiviral|Antivirals]] - If your Hashimoto's was triggered by a bacterial or viral infection, then suppressing the infection using antiviral treatment might improve symptoms.
* [[Epstein-Barr virus#Treatment|Epstein-Barr virus treatment]]
* [[Human herpesvirus 6#Antivirals|HHV-6 treatment]]

=== Supplementation ===
[[Selenium]] - Selenium has been shown to decrease thyroperoxidase (TPO) antibody levels and improve overall symptoms associated with Hashimoto's Thyroiditis.<ref>{{Cite journal|last=Ventura|first=Mara|last2=Melo|first2=Miguel|last3=Carrilho|first3=Francisco|date=2017|title=Selenium and Thyroid Disease: From Pathophysiology to Treatment|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307254/|journal=International Journal of Endocrinology|volume=2017|doi=10.1155/2017/1297658|issn=1687-8337|pmc=5307254|pmid=28255299}}</ref><ref>{{Cite journal|last=van Zuuren|first=Esther J.|last2=Albusta|first2=Amira Y.|last3=Fedorowicz|first3=Zbys|last4=Carter|first4=Ben|last5=Pijl|first5=Hanno|date=Mar 2014|title=Selenium Supplementation for Hashimoto's Thyroiditis: Summary of a Cochrane Systematic Review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005265/|journal=European Thyroid Journal|volume=3|issue=1|pages=25–31|doi=10.1159/000356040|issn=2235-0640|pmc=4005265|pmid=24847462|quote=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> A 2017 study demonstrated that the combination of Selenium and Myo-inositol had an even greater effect.<ref>{{Cite journal|last=Nordio|first=M.|last2=Basciani|first2=S.|date=Jun 2017|title=Myo-inositol plus selenium supplementation restores euthyroid state in Hashimoto's patients with subclinical hypothyroidism|url=https://pubmed.ncbi.nlm.nih.gov/28724185/|journal=European Review for Medical and Pharmacological Sciences|volume=21|issue=2 Suppl|pages=51–59|issn=2284-0729|pmid=28724185|doi=|pmc=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

Supplements most commonly used to treat Epstein-Barr Virus (EBV) triggered Hashimoto's include:
* [[Olive leaf and olives|Olive leaf extract]]
* Lauricidin/Monolaurin
* [[Licorice|Licorice root]] (glycyrrhizic acid)
* [[St. John’s Wort|St. John’s wort]]
* [[Echinacea]]
* [[Vitamin C]]
* [[Vitamin D]]

=== Immunomodulator ===
[[Low dose naltrexone|Low-dose naltrexone (LDN)]] - LDN is an immunomodulating medication that many claim has improved their Hashimoto's symptoms. However, there is a lack of scientific studies to back up this claim.

==See also==
* [[Autoimmune disease]]
* [[Female predominant diseases]]
* [[Triiodothyronine]]
* [[Thyroid disease]]
* [[Thyroid gland]]
* [[Thyroxine]]

==Learn more==
*[http://www.thyroiduk.org.uk/tuk/about_the_thyroid/hashimotos.html Hashimoto's] - Thyroid UK

==References==
{{reflist}}

[[Category:Diagnoses]]
[[Category:Potential comorbidities]]
[[Category:Thyroid diseases]]

Hypothyroidism

2020-11-25T20:46:44Z

Fireballsky:Fixing redirect

#REDIRECT [[Hashimoto's thyroiditis (hypothyroidism)]]

Hypothyroidism

2020-11-25T20:45:03Z

Fireballsky:Redirecting to Hashimoto's thyroiditis (hypothyroidism)

#REDIRECT [[Hashimoto's thyroiditis (hypothyroidism)]] {{R from merge}}

Autoantibody

2020-11-25T02:17:31Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|<ref name=":11" />
|
|
|-
|'''Cytoplasmic membrane antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />

68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>

<ref name=":12">{{Cite journal|last=Hilgers|first=A.|last2=Frank|first2=J.|date=1994|title=[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes]|url=https://pubmed.ncbi.nlm.nih.gov/7856214/|journal=Wiener Medizinische Wochenschrift (1946)|volume=144|issue=16|pages=399–406|issn=0043-5341|pmid=7856214}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|TPO
|<ref name=":12" />
|
|
|-
|
|
|
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Cytokine

2020-11-25T02:14:13Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|'''Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.'''
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|'''Promote the growth of immune system cells and help regulate the immune system'''
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response, and activates antigen presenting cells

Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “[[sickness behavior]]".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates [[T cell|T-Cell]] growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates [[Eosinophil|eosinophils]] in the bone marrow during inflammation
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and [[autoantibody]] production

An important inflammatory cytokine and [[Hypothalamic-pituitary-adrenal axis|HPA axis]] modulator. IL-6 also plays a role in other CFS symptoms including [[hyperalgesia]], [[fatigue]], [[Sleep dysfunction|sleep impairment]], and [[depression]].

It has been reported that IL-6 induces excessive daytime sleepiness or disturbed [[Unrefreshing sleep|non-refreshing sleep]] in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>

IL-6 also directly increases glucose metabolism in human skeletal muscle<ref>{{Cite journal|last=Glund|first=Stephan|last2=Deshmukh|first2=Atul|last3=Long|first3=Yun Chau|last4=Moller|first4=Theodore|last5=Koistinen|first5=Heikki A.|last6=Caidahl|first6=Kenneth|last7=Zierath|first7=Juleen R.|last8=Krook|first8=Anna|date=2007-06-01|title=Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle|url=https://diabetes.diabetesjournals.org/content/56/6/1630|journal=Diabetes|language=en|volume=56|issue=6|pages=1630–1637|doi=10.2337/db06-1733|issn=0012-1797|pmid=17363741}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates [[adaptive immune system]], and tumor cell apoptosis
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily [[Neutrophil|neutrophils]] to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes [[mast cell]] growth, stimulates cell proliferation and cytotoxicity, and is involved in apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to [[Pathogen|pathogens]]
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates [[inflammation]], and function of B-cells and T-cells.

IL-11 inhibits tissue inflammation<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, [[Natural killer cell|NK cells]], and [[Cytotoxic T cell|CTLs]]. IL-12 is a critical link between the innate and adaptive immunity<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response ([[B cell|B-cells]] and [[Monocyte|monocytes]]). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells, and increases anti-tumor activities<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|'''Regulate inflammatory and immune responses'''
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" /><ref>{{Cite journal|last=Hilgers|first=A.|last2=Frank|first2=J.|date=1994|title=[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes]|url=https://pubmed.ncbi.nlm.nih.gov/7856214/|journal=Wiener Medizinische Wochenschrift (1946)|volume=144|issue=16|pages=399–406|issn=0043-5341|pmid=7856214}}</ref>

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates [[Innate immune system|innate immune]] response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|'''Direct cell migration, adhesion and activation'''
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24 or eotaxin-2)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1 or fractalkine'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colony Stimulating Factors'''
|'''Promote cell proliferation and differentiation'''
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and [[Macrophage|macrophages]]<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of [[Granulocyte|granulocytes]] and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|'''Regulation of immune cells'''
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to [[Mitochondrial disorder|mitochondrial disorders]] and skeletal [[Muscle fatigability|muscle fatigue]]<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a [[hormone]] and cytokine. Critical in [[Metabolic features of chronic fatigue syndrome|metabolic function]]. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Autoantibody

2020-11-24T04:13:47Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|<ref name=":11" />
|
|
|-
|'''Cytoplasmic membrane antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T04:03:57Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|<ref name=":11" />
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
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|-
|
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|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
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|-
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|-
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|-
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|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:58:04Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|'''Neurotransmitter receptors'''
|
|
|
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|
|
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|<ref name=":11" />
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|-
|
|
|
|
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8" /><ref name=":10" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:54:54Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Nuclear envelope autoantibodies'''
|
|
|
|-
|Lamin B1 (intermediate filament)
|<ref name=":11" />
|
|
|-
|Cytoplasmic proteins (intermediate filament)
|<ref name=":11" />
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref name=":11">{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8" />
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:49:49Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|dUTPase
|<ref>{{Cite journal|last=Halpin|first=Peter|last2=Williams|first2=Marshall Vance|last3=Klimas|first3=Nancy G.|last4=Fletcher|first4=Mary Ann|last5=Barnes|first5=Zachary|last6=Ariza|first6=Maria Eugenia|date=2017|title=Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810|journal=Journal of Medical Virology|language=en|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc=PMC5513753|pmid=28303641}}</ref>
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref>{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8" />
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:48:09Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|
|
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref>{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8" />
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" /><ref name=":10" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:40:58Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|
|
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref><ref name=":10">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|last5=Twisk|first5=Frank N. M.|last6=Geffard|first6=Michel|date=2012-12|title=IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression|url=https://pubmed.ncbi.nlm.nih.gov/22614823/|journal=Metabolic Brain Disease|volume=27|issue=4|pages=415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref>
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref>{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8" />
|
|
|-
|Palmitic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|Myristic acid
|<ref name=":8" /><ref name=":10" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:35:44Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|
|
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|Endothelial cells
|30% (24 of 81)<ref name=":9">{{Cite journal|last=Ortega‐Hernandez|first=Oscar-Danilo|last2=Cuccia|first2=Mariaclara|last3=Bozzini|first3=Sara|last4=Bassi|first4=Nicola|last5=Moscavitch|first5=Samuel|last6=Diaz‐Gallo|first6=Lina-Marcela|last7=Blank|first7=Miri|last8=Agmon‐Levin|first8=Nancy|last9=Shoenfeld|first9=Yehuda|date=2009|title=Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome|url=https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x|journal=Annals of the New York Academy of Sciences|language=en|volume=1173|issue=1|pages=589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref>
|
|
|-
|Neuronal cells
|16% (13 of 81) <ref name=":9" />
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|Oxidized LDL (oxLDL)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Kubera|first2=Marta|last3=Uytterhoeven|first3=Marc|last4=Vrydags|first4=Nicolas|last5=Bosmans|first5=Eugene|date=2011-04|title=Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://pubmed.ncbi.nlm.nih.gov/21455120/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=17|issue=4|pages=SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref>
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref>{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8" />
|
|
|-
|Palmitic acid
|<ref name=":8" />
|
|
|-
|Myristic acid
|<ref name=":8" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:29:02Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

An '''autoantibody''' is a type of antibody created by the immune system which targets the organism's own tissues, cells, or cell components. Many autoimmune diseases are caused by autoantibodies.

[[Category:Body systems]]

== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH ==
Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH.
{| class="wikitable"
|+Autoantibodies Found in ME/CFS, POTS and OH
!Autoantibody target
!ME/CFS
!POTS
!OH
|-
|Adrenergic receptor alpha 1
|
|Yes<ref name=":0">{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde-Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-02-26|title=Autoimmune basis for postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24572257|journal=Journal of the American Heart Association|volume=3|issue=1|pages=e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref>
|
|-
|Adrenergic receptor alpha 2
|
|
|
|-
|Adrenergic receptor beta 1
|
|Yes<ref name=":0" />
|Yes<ref name=":1">{{Cite journal|last=Yu|first=Xichun|last2=Stavrakis|first2=Stavros|last3=Hill|first3=Michael A.|last4=Huang|first4=Shijun|last5=Reim|first5=Sean|last6=Li|first6=Hongliang|last7=Khan|first7=Muneer|last8=Hamlett|first8=Sean|last9=Cunningham|first9=Madeleine W.|date=Jan 2012|title=Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension|url=https://www.ncbi.nlm.nih.gov/pubmed/22130180|journal=Journal of the American Society of Hypertension: JASH|volume=6|issue=1|pages=40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref>
|-
|Adrenergic receptor beta 2
|Elevated<ref name=":2">{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>
|Yes<ref name=":0" />
|Yes<ref name=":1" />
|-
|
|
|
|
|-
|Muscarinic acetylcholine receptor M1
|53% (32 of 60)<ref name=":3">{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=Aug 2003|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12851722|journal=International Journal of Molecular Medicine|volume=12|issue=2|pages=225–230|issn=1107-3756|pmid=12851722}}</ref>
|Yes<ref name=":5">{{Cite web|url=http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf|title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker|last=Dubey|first=Divyanshu|last2=Hopkins|first2=Steve|date=|website=|archive-url=|archive-date=|dead-url=|access-date=|last3=Vernino|first3=Steven}}</ref>
|
|-
|Muscarinic acetylcholine receptor M2
|
|Yes<ref name=":5" />
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M3
|Elevated<ref name=":2" />
|
|Yes<ref name=":1" />
|-
|Muscarinic acetylcholine receptor M4
|Elevated<ref name=":2" />
|
|
|-
|NO-Bovine serum albumin (nitro-BSA)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Kubera|first3=Marta|last4=Leunis|first4=Jean-Claude|date=2008-06|title=An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS|url=https://pubmed.ncbi.nlm.nih.gov/18580855/|journal=Neuro Endocrinology Letters|volume=29|issue=3|pages=313–319|issn=0172-780X|pmid=18580855}}</ref>
|
|
|-
|
|
|
|
|-
|
|
|
|
|-
|S-farnesyl-L-cysteine
|<ref name=":8">{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=2006-10|title=Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins|url=https://pubmed.ncbi.nlm.nih.gov/17159817/|journal=Neuro Endocrinology Letters|volume=27|issue=5|pages=615–621|issn=0172-780X|pmid=17159817}}</ref>
|
|
|-
|
|
|
|
|-
|Nicotinic ganglionic acetylcholine receptor alpha 3
|
|Yes<ref name=":6">{{Cite journal|last=Watari|first=Mari|last2=Nakane|first2=Shunya|last3=Mukaino|first3=Akihiro|last4=Nakajima|first4=Makoto|last5=Mori|first5=Yukiko|last6=Maeda|first6=Yasuhiro|last7=Masuda|first7=Teruaki|last8=Takamatsu|first8=Koutaro|last9=Kouzaki|first9=Yanosuke|date=2018-02-28|title=Autoimmune postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/|journal=Annals of Clinical and Translational Neurology|volume=5|issue=4|pages=486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref>
|
|-
|Nicotinic ganglionic acetylcholine receptor beta 4
|
|Yes<ref name=":6" />
|
|-
|68/48 kDa protein
|13% (15 of 114); 0% controls<ref>{{Cite journal|last=Nishikai|first=M.|last2=Tomomatsu|first2=S.|last3=Hankins|first3=R. W.|last4=Takagi|first4=S.|last5=Miyachi|first5=K.|last6=Kosaka|first6=S.|last7=Akiya|first7=K.|date=2001-07|title=Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders|url=https://pubmed.ncbi.nlm.nih.gov/11477286/|journal=Rheumatology (Oxford, England)|volume=40|issue=7|pages=806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref>
|
|
|-
|Angiotensin II type 1 receptor
|
|Yes<ref>{{Cite journal|last=Yu|first=Xichun|last2=Li|first2=Hongliang|last3=Murphy|first3=Taylor A.|last4=Nuss|first4=Zachary|last5=Liles|first5=Jonathan|last6=Liles|first6=Campbell|last7=Aston|first7=Christopher E.|last8=Raj|first8=Satish R.|last9=Fedorowski|first9=Artur|date=2018-04-04|title=Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29618472|journal=Journal of the American Heart Association|volume=7|issue=8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref>
|
|-
|Mu-opioid receptor
|15% (9 of 60)<ref name=":3" />
|
|
|-
|Serotonin or 5-hydroxytryptamine (5-HT)
|62% (26 of 42)<ref name=":4">{{Cite journal|last=Klein|first=R.|last2=Berg|first2=P. A.|date=1995-10-16|title=High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/9392689|journal=European Journal of Medical Research|volume=1|issue=1|pages=21–26|issn=0949-2321|pmid=9392689}}</ref>

|
|
|-
|Gangliosides
|43% (18 of 42)<ref name=":4" />
|
|
|-
|Antineutrophil cytoplasmic antibodies (ANCA)
|47% (28 of 60)<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9041942|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>
|
|
|-
|HSP60 (Chlamydia pneumoniae peptide)
|24% IgM 15 of 61)<ref>{{Cite journal|last=Elfaitouri|first=Amal|last2=Herrmann|first2=Björn|last3=Bölin-Wiener|first3=Agnes|last4=Wang|first4=Yilin|last5=Gottfries|first5=Carl-Gerhard|last6=Zachrisson|first6=Olof|last7=Pipkorn|first7=Rϋdiger|last8=Rönnblom|first8=Lars|last9=Blomberg|first9=Jonas|date=2013|title=Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24312270/|journal=PloS One|volume=8|issue=11|pages=e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref>
|
|
|-
|Microtubule-associated protein 2 (MAP2)
|<ref name=":7">{{Cite journal|last=Vernon|first=Suzanne D|last2=Reeves|first2=William C|date=2005-05-25|title=Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/|journal=Journal of Autoimmune Diseases|volume=2|pages=5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref>
|
|
|-
|'''Antiphospholipid antibodies'''
|
|
|
|-
|Phospholipids (All)
|38% (16 of 42)<ref name=":4" />
|
|
|-
|Cardiolipin
|95% (38 of 40)<ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Campora|first2=Cara Empey|last3=Hara|first3=Cynthia|last4=Kuribayashi|first4=Tina|last5=Le Huynh|first5=Diana|last6=Yabusaki|first6=Kenichi|date=2009|title=Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19623655|journal=Journal of Clinical Laboratory Analysis|volume=23|issue=4|pages=210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal|last=Hokama|first=Yoshitsugi|last2=Empey‐Campora|first2=Cara|last3=Hara|first3=Cynthia|last4=Higa|first4=Nicole|last5=Siu|first5=Nathaniel|last6=Lau|first6=Rachael|last7=Kuribayashi|first7=Tina|last8=Yabusaki|first8=Kenichi|date=2008|title=Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217|journal=Journal of Clinical Laboratory Analysis|language=en|volume=22|issue=2|pages=99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc=PMC6649096|pmid=18348309}}</ref>
|
|
|-
|β2 glycoprotein
|
|
|
|-
|Phosphatidylinositol (PI)
|<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=2007-12|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://pubmed.ncbi.nlm.nih.gov/18063934/|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref>
|
|
|-
|
|
|
|
|-
|'''Antinuclear autoantibodies (ANA)'''
|
|
|
|-
|ANA (All)
|56.7% (34 of 60)<ref name=":3" />68% (41 of 60); 15% controls<ref>{{Cite journal|last=Konstantinov|first=K|last2=von Mikecz|first2=A|last3=Buchwald|first3=D|last4=Jones|first4=J|last5=Gerace|first5=L|last6=Tan|first6=E M|date=1996-10-15|title=Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/|journal=Journal of Clinical Investigation|volume=98|issue=8|pages=1888–1896|issn=0021-9738|pmid=8878441}}</ref>
|
|
|-
|ssDNA (single-stranded DNA)
|<ref name=":7" />
|
|
|-
|dsDNA (double-stranded DNA)
|
|
|
|-
|
|
|
|
|-
|'''Fatty Acid autoantibodies'''
|
|
|
|-
|Oleic acid
|<ref name=":8" />
|
|
|-
|Palmitic acid
|<ref name=":8" />
|
|
|-
|Myristic acid
|<ref name=":8" />
|
|
|-
|'''Lipid peroxidation by-products'''
|
|
|
|-
|Malondialdehyde (MDA)
|<ref name=":8" />
|
|
|-
|Azelaic acid
|<ref name=":8" />
|
|
|-
|'''N-oxide modified amino-acids'''
|
|
|
|-
|NO-tyrosine
|<ref name=":8" />
|
|
|-
|NO-phenylalanine
|<ref name=":8" />
|
|
|-
|NO-arginine
|<ref name=":8" />
|
|
|-
|NO-tryptophan
|<ref name=":8" />
|
|
|-
|NO-cysteinyl
|<ref name=":8" />
|
|
|}

== Learn more ==

* [https://en.wikipedia.org/wiki/Autoantibody Autoantibody (Wikipedia)]
* [https://en.wikipedia.org/wiki/Hypersensitivity Hypersensitivity reactions (Wikipedia)]

== References ==

<references />
[[Category:Immunology]]

Autoantibody

2020-11-24T03:24:44Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-24T02:55:25Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Cytokine

2020-11-22T18:44:23Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|'''Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.'''
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|'''Promote the growth of immune system cells and help regulate the immune system'''
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response, and activates antigen presenting cells

Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “[[sickness behavior]]".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates [[T cell|T-Cell]] growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates [[Eosinophil|eosinophils]] in the bone marrow during inflammation
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and [[autoantibody]] production

An important inflammatory cytokine and [[Hypothalamic-pituitary-adrenal axis|HPA axis]] modulator. IL-6 also plays a role in other CFS symptoms including [[hyperalgesia]], [[fatigue]], [[Sleep dysfunction|sleep impairment]], and [[depression]].

It has been reported that IL-6 induces excessive daytime sleepiness or disturbed [[Unrefreshing sleep|non-refreshing sleep]] in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>

IL-6 also directly increases glucose metabolism in human skeletal muscle<ref>{{Cite journal|last=Glund|first=Stephan|last2=Deshmukh|first2=Atul|last3=Long|first3=Yun Chau|last4=Moller|first4=Theodore|last5=Koistinen|first5=Heikki A.|last6=Caidahl|first6=Kenneth|last7=Zierath|first7=Juleen R.|last8=Krook|first8=Anna|date=2007-06-01|title=Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle|url=https://diabetes.diabetesjournals.org/content/56/6/1630|journal=Diabetes|language=en|volume=56|issue=6|pages=1630–1637|doi=10.2337/db06-1733|issn=0012-1797|pmid=17363741}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates [[adaptive immune system]], and tumor cell apoptosis
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily [[Neutrophil|neutrophils]] to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes [[mast cell]] growth, stimulates cell proliferation and cytotoxicity, and is involved in apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to [[Pathogen|pathogens]]
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates [[inflammation]], and function of B-cells and T-cells.

IL-11 inhibits tissue inflammation<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, [[Natural killer cell|NK cells]], and [[Cytotoxic T cell|CTLs]]. IL-12 is a critical link between the innate and adaptive immunity<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response ([[B cell|B-cells]] and [[Monocyte|monocytes]]). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells, and increases anti-tumor activities<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|'''Regulate inflammatory and immune responses'''
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates [[Innate immune system|innate immune]] response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|'''Direct cell migration, adhesion and activation'''
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24 or eotaxin-2)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1 or fractalkine'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colony Stimulating Factors'''
|'''Promote cell proliferation and differentiation'''
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and [[Macrophage|macrophages]]<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of [[Granulocyte|granulocytes]] and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|'''Regulation of immune cells'''
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to [[Mitochondrial disorder|mitochondrial disorders]] and skeletal [[Muscle fatigability|muscle fatigue]]<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a [[hormone]] and cytokine. Critical in [[Metabolic features of chronic fatigue syndrome|metabolic function]]. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Autoantibody

2020-11-22T05:14:34Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T05:01:47Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T05:00:43Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:57:52Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:54:22Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:49:23Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:45:26Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:37:49Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:34:35Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T04:13:26Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Autoantibody

2020-11-22T03:51:13Z

Fireballsky:/* Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH */

Cytokine

2020-11-22T03:11:55Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|'''Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.'''
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|'''Promote the growth of immune system cells and help regulate the immune system'''
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “[[sickness behavior]]".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates [[T cell|T-Cell]] growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates [[Eosinophil|eosinophils]] in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and [[autoantibody]] production

An important inflammatory cytokine and [[Hypothalamic-pituitary-adrenal axis|HPA axis]] modulator. IL-6 also plays a role in other CFS symptoms including [[hyperalgesia]], [[fatigue]], [[Sleep dysfunction|sleep impairment]], and [[depression]].

It has been reported that IL-6 induces excessive daytime sleepiness or disturbed [[Unrefreshing sleep|non-refreshing sleep]] in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>

IL-6 also directly increases glucose metabolism in human skeletal muscle<ref>{{Cite journal|last=Glund|first=Stephan|last2=Deshmukh|first2=Atul|last3=Long|first3=Yun Chau|last4=Moller|first4=Theodore|last5=Koistinen|first5=Heikki A.|last6=Caidahl|first6=Kenneth|last7=Zierath|first7=Juleen R.|last8=Krook|first8=Anna|date=2007-06-01|title=Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle|url=https://diabetes.diabetesjournals.org/content/56/6/1630|journal=Diabetes|language=en|volume=56|issue=6|pages=1630–1637|doi=10.2337/db06-1733|issn=0012-1797|pmid=17363741}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates [[adaptive immune system]]
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily [[Neutrophil|neutrophils]] to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes [[mast cell]] growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to [[Pathogen|pathogens]]
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates [[inflammation]]. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, [[Natural killer cell|NK cells]], and [[Cytotoxic T cell|CTLs]]<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response ([[B cell|B-cells]] and [[Monocyte|monocytes]]). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|'''Regulate inflammatory and immune responses'''
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates [[Innate immune system|innate immune]] response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|'''Direct cell migration, adhesion and activation'''
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24 or eotaxin-2)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1 or fractalkine'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colony Stimulating Factors'''
|'''Promote cell proliferation and differentiation'''
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and [[Macrophage|macrophages]]<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of [[Granulocyte|granulocytes]] and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|'''Regulation of immune cells'''
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to [[Mitochondrial disorder|mitochondrial disorders]] and skeletal [[Muscle fatigability|muscle fatigue]]<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a [[hormone]] and cytokine. Critical in [[Metabolic features of chronic fatigue syndrome|metabolic function]]. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-22T02:01:59Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “[[sickness behavior]]".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates [[T cell|T-Cell]] growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates [[Eosinophil|eosinophils]] in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and [[autoantibody]] production

An important inflammatory cytokine and [[Hypothalamic-pituitary-adrenal axis|HPA axis]] modulator. IL-6 also plays a role in other CFS symptoms including [[hyperalgesia]], [[fatigue]], [[Sleep dysfunction|sleep impairment]], and [[depression]].

It has been reported that IL-6 induces excessive daytime sleepiness or disturbed [[Unrefreshing sleep|non-refreshing sleep]] in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>

IL-6 also directly increases glucose metabolism in human skeletal muscle<ref>{{Cite journal|last=Glund|first=Stephan|last2=Deshmukh|first2=Atul|last3=Long|first3=Yun Chau|last4=Moller|first4=Theodore|last5=Koistinen|first5=Heikki A.|last6=Caidahl|first6=Kenneth|last7=Zierath|first7=Juleen R.|last8=Krook|first8=Anna|date=2007-06-01|title=Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle|url=https://diabetes.diabetesjournals.org/content/56/6/1630|journal=Diabetes|language=en|volume=56|issue=6|pages=1630–1637|doi=10.2337/db06-1733|issn=0012-1797|pmid=17363741}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates [[adaptive immune system]]
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily [[Neutrophil|neutrophils]] to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes [[mast cell]] growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to [[Pathogen|pathogens]]
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates [[inflammation]]. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, [[Natural killer cell|NK cells]], and [[Cytotoxic T cell|CTLs]]<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response ([[B cell|B-cells]] and [[Monocyte|monocytes]]). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates [[Innate immune system|innate immune]] response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24 or eotaxin-2)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1 or fractalkine'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and [[Macrophage|macrophages]]<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of [[Granulocyte|granulocytes]] and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to [[Mitochondrial disorder|mitochondrial disorders]] and skeletal [[Muscle fatigability|muscle fatigue]]<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a [[hormone]] and cytokine. Critical in [[Metabolic features of chronic fatigue syndrome|metabolic function]]. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-22T00:29:02Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “[[sickness behavior]]".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates [[T cell|T-Cell]] growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates [[Eosinophil|eosinophils]] in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and [[autoantibody]] production

An important inflammatory cytokine and [[Hypothalamic-pituitary-adrenal axis|HPA axis]] modulator. IL-6 also plays a role in other CFS symptoms including [[hyperalgesia]], [[fatigue]], [[Sleep dysfunction|sleep impairment]], and [[depression]].

It has been reported that IL-6 induces excessive daytime sleepiness or disturbed [[Unrefreshing sleep|non-refreshing sleep]] in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates [[adaptive immune system]]
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily [[Neutrophil|neutrophils]] to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes [[mast cell]] growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to [[Pathogen|pathogens]]
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates [[inflammation]]. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, [[Natural killer cell|NK cells]], and [[Cytotoxic T cell|CTLs]]<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response ([[B cell|B-cells]] and [[Monocyte|monocytes]]). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates [[Innate immune system|innate immune]] response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24 or eotaxin-2)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1 or fractalkine'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and [[Macrophage|macrophages]]<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of [[Granulocyte|granulocytes]] and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to [[Mitochondrial disorder|mitochondrial disorders]] and skeletal [[Muscle fatigability|muscle fatigue]]<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a [[hormone]] and cytokine. Critical in [[Metabolic features of chronic fatigue syndrome|metabolic function]]. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T23:52:52Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “[[sickness behavior]]".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates [[T cell|T-Cell]] growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates [[Eosinophil|eosinophils]] in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and [[autoantibody]] production

An important inflammatory cytokine and [[Hypothalamic-pituitary-adrenal axis|HPA axis]] modulator. IL-6 also plays a role in other CFS symptoms including [[hyperalgesia]], [[fatigue]], [[Sleep dysfunction|sleep impairment]], and [[depression]].

It has been reported that IL-6 induces excessive daytime sleepiness or disturbed [[Unrefreshing sleep|non-refreshing sleep]] in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates [[adaptive immune system]]
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily [[Neutrophil|neutrophils]] to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes [[mast cell]] growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to [[Pathogen|pathogens]]
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates [[inflammation]]. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, [[Natural killer cell|NK cells]], and [[Cytotoxic T cell|CTLs]]<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response ([[B cell|B-cells]] and [[Monocyte|monocytes]]). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates [[Innate immune system|innate immune]] response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and [[Macrophage|macrophages]]<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of [[Granulocyte|granulocytes]] and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to [[Mitochondrial disorder|mitochondrial disorders]] and skeletal [[Muscle fatigability|muscle fatigue]]<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a [[hormone]] and cytokine. Critical in [[Metabolic features of chronic fatigue syndrome|metabolic function]]. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T23:27:47Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and autoantibody production

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8 or CXCL8 C-X-C motif chemokine ligand 8'')

Regulates inflammatory response by orchestrating the migration of primarily neutrophils to the site of infection. IL-8 has also been shown to be involved in cell proliferation, and tissue remodeling<ref>{{Cite journal|last=El Ayadi|first=Amina|last2=Herndon|first2=David N.|last3=Finnerty|first3=Celeste C.|date=2018-01-01|editor-last=Herndon|editor-first=David N.|title=21 - Biomarkers in Burn Patient Care|url=http://www.sciencedirect.com/science/article/pii/B9780323476614000216|language=en|publisher=Elsevier|pages=232–235.e2|isbn=978-0-323-47661-4}}</ref>
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T23:12:06Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and autoantibody production

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref><ref>{{Cite journal|last=Sorenson|first=Matthew|last2=Jason|first2=Leonard|last3=Lerch|first3=Athena|last4=Porter|first4=Nicole|last5=Peterson|first5=Jonna|last6=Mathews|first6=Herbert|date=2012-03-02|title=The Production of Interleukin-8 is Increased in Plasma and Peripheral Blood Mononuclear Cells of Patients with Fatigue|url=https://m.scirp.org/papers/abstract/17756|journal=Neuroscience and Medicine|language=en|volume=3|issue=1|pages=720–726|doi=10.4236/nm.2012.31007}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T23:00:13Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system, cellular proliferation and differentiation, and autoantibody production

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:56:49Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>

IL-1β is a pro-inflammatory cytokine with metabolic and immuno-inflammatory functions.<ref name=":8" />
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:24:44Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>

Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />

Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:21:38Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref name=":28">{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref name=":28" />
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:18:22Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref name=":27">{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref name=":27" /><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:15:35Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref name=":26">{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref name=":26" />

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:14:25Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref name=":25" />
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:12:50Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref name=":24" /><ref name=":6" />

Increased post-exercise<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:11:37Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref name=":24">{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref name=":24" />
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Decreased IL-23p40<ref name=":24" />
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":6" />

Increased post-exercise<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref name=":24" />
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]

Cytokine

2020-11-21T22:09:01Z

Fireballsky:/* Table of Cytokines */

'''Cytokines''' are any class of immunoregulatory [[:Category:Proteins|proteins]] secreted by cells, especially [[Immune cell|immune system cells]].<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/cytokine#medicalDictionary|title=Definition of CYTOKINE|last=Merriam-Webster Medical Dictionary|first=|date=|website=www.merriam-webster.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-10-06}}</ref> Cytokines are small proteins important in cell signaling that modulate the [[immune system]].

There are many different cytokines. They function as messenger molecules passing information around the body. They resemble [[hormone]]s in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.

==Types of cytokines==

*[[Chemokine]]s
*[[Interferon]]s
*[[Interleukin]]s
*[[Lymphokine]]s
*[[TNF-alpha |Tumor necrosis factor]]

==Cellular immune response==

[[IFN-γ]], [[TNF-alpha|TNFα]]

==Antibody response==

[[TGF-beta|TGF-β]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], [[Interleukin 13|IL-13]]

==Role in human disease==

===Chronic Fatigue Syndrome===

There is increasing evidence that cytokine expression is altered in CFS (ME). [[Mady Hornig]] et al (2015) indicates that there is a generally increased response in the first 3 years of illness.<ref name="Hornig, 2015" /> In 2017, a [[Jose Montoya|Montoya]], et al, study showed that "seventeen cytokines had a statistically significant upward linear trend that correlated with [[ME/CFS]] severity"..."thirteen of these are proinflammatory, likely contributing to many of the symptoms experienced by patients."<ref name=":11" />

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). <ref name="Landi2015" /> It is worth noting that these differences can average each other out when data from newly diagnosed and long term patients are analysed together. More accurate data may necessitate patient groups being stratified by disease duration.

In a 2017 study by Hornig, Lipkin et al, 51 Cytokines of cerebrospinal fluid were measured where they found Atypical and Classical cases of [[ME/CFS]]. There are differing immune signatures within the [[central nervous system]]. "Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses."<ref>{{Cite journal|last=Lipkin|first=W. I.|author-link=Ian Lipkin|last2=Peterson|first2=D. L.|author-link2=Daniel Peterson|last3=Ukaigwe|first3=J. E.|author-link3=J Ukaigwe|last4=Che|first4=X.|author-link4=X Che|last5=Eddy|first5=M. L.|author-link5=Meredith Eddy|last6=Gottschalk|first6=C. G.|last7=Hornig|first7=M.|date=Apr 2017|title=Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations|url=https://www.nature.com/articles/tp201744|journal=Translational Psychiatry|language=en|volume=7|issue=4|pages=e1080|doi=10.1038/tp.2017.44|issn=2158-3188|quote=|via=}}</ref>

When reading cytokine studies it is important to remember that with so many cytokines it is common to find some pattern and results can change quickly within individuals. In a small sample, if just a couple of people were fighting a cold then this could change the overall results.

===Fibromyalgia===

[[Fibromyalgia]]: Cytokines [[IL-1beta]], [[Interleukin 6|IL-6]] and [[TNF-alpha]] are involved with central and peripheral neuropathic pain which is experienced by [[Fibromyalgia]] patients.<ref>{{Cite journal|last=Staud|first=Roland|author-link=Roland Staud|author-link2=|author-link3=|author-link4=|author-link5=|date=Mar 2004|title=Fibromyalgia pain: do we know the source?|url=https://www.ncbi.nlm.nih.gov/pubmed/14770104/|journal=Current Opinion in Rheumatology|volume=16|issue=2|pages=157–163|issn=1040-8711|pmid=14770104|quote=|via=|last2=|first2=|doi=|pmc=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|access-date=|author-link6=}}</ref> Profiles are distinguishing [[Systemic lupus erythematosus|Lupus]] and [[Rheumatoid arthritis|Rheumatoid Arthritis]] from Fibromyalgia.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM]</ref>

=== Table of Cytokines ===
{| class="wikitable"
!Cytokine
!Description
!Increased in ME/CFS
!Decreased in ME/CFS
|-
|'''[[Interferon|Interferons]]'''
|Interferons are antiviral agents that modulate the immune system. They stimulate [[Natural killer cell|Natural killer cells]] and [[Macrophage|macrophages]] to elicit antiviral and anti-tumor responses.
|
|
|-
|[[IFN-α]]
|(''Interferon alpha'')

A type I interferon produced by [[Leucocyte|Leucocytes.]] Major contributor to innate immunity against viral infection.
|Increased<ref>{{Cite journal|last=Lever|first=A. M. L.|last2=Lewis|first2=D. M.|last3=Bannister|first3=B. A.|last4=Fry|first4=M.|last5=Berry|first5=N.|date=1988-07-09|title=INTERFERON PRODUCTION IN POSTVIRAL FATIGUE SYNDROME|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)90029-3/abstract|journal=The Lancet|language=English|volume=332|issue=8602|pages=101|doi=10.1016/S0140-6736(88)90029-3|issn=0140-6736}}</ref><ref>{{Cite journal|last=Vojdani|first=A.|last2=Ghoneum|first2=M.|last3=Choppa|first3=P. C.|last4=Magtoto|first4=L.|last5=Lapp|first5=C. W.|date=1997|title=Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.1997.tb00019.x|journal=Journal of Internal Medicine|language=en|volume=242|issue=6|pages=465–478|doi=10.1111/j.1365-2796.1997.tb00019.x|issn=1365-2796}}</ref>
|
|-
|[[IFN-β]]
|(''Interferon beta'')

A type I interferon produced in [[Fibroblast|fibroblasts]] by [[RNAseL]]. It is used to reduce relapses in relapsing-remitting [[multiple sclerosis]]. Major contributor to innate immunity against viral infection.
|
|
|-
|IFN-κ
|(''Interferon kappa'')

A type I interferon
|
|
|-
|[[IFN-γ]]
|(''Interferon gamma'')

The only Type II interferon in humans, it is produced by [[T cell]]s and [[Natural killer cell|natural killer cell]]s. Critical to both innate and adaptive immunity. Promotes macrophage activation.
|Increased<ref name=":5">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Don R.|last4=Ashton|first4=Kevin J.|last5=Ramos|first5=Sandra B.|last6=Keane|first6=James|last7=Klimas|first7=Nancy G.|last8=Marshall-Gradisnik|first8=Sonya M.|date=2011-05-28|title=Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://doi.org/10.1186/1479-5876-9-81|journal=Journal of Translational Medicine|volume=9|issue=1|pages=81|doi=10.1186/1479-5876-9-81|issn=1479-5876|pmc=PMC3120691|pmid=21619669}}</ref><ref name=":6">{{Cite journal|last=Brenu|first=Ekua W.|last2=van Driel|first2=Mieke L.|last3=Staines|first3=Donald R.|last4=Ashton|first4=Kevin J.|last5=Hardcastle|first5=Sharni L.|last6=Keane|first6=James|last7=Tajouri|first7=Lotti|last8=Peterson|first8=Daniel|last9=Ramos|first9=Sandra B.|date=2012-05-09|title=Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis|url=https://doi.org/10.1186/1479-5876-10-88|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=88|doi=10.1186/1479-5876-10-88|issn=1479-5876|pmc=PMC3464733|pmid=22571715}}</ref><ref name=":7">{{Cite journal|last=Garcia|first=Melissa N.|last2=Hause|first2=Anne M.|last3=Walker|first3=Christopher M.|last4=Orange|first4=Jordan S.|last5=Hasbun|first5=Rodrigo|last6=Murray|first6=Kristy O.|date=2014-07-25|title=Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines|url=https://www.liebertpub.com/doi/abs/10.1089/vim.2014.0035|journal=Viral Immunology|volume=27|issue=7|pages=327–333|doi=10.1089/vim.2014.0035|issn=0882-8245|pmc=PMC4150370|pmid=25062274}}</ref><ref name=":16">{{Cite journal|last=Khaiboullina|first=Svetlana F.|last2=DeMeirleir|first2=Kenny L.|last3=Rawat|first3=Shanti|last4=Berk|first4=Grady S.|last5=Gaynor-Berk|first5=Rory S.|last6=Mijatovic|first6=Tatjana|last7=Blatt|first7=Natalia|last8=Rizvanov|first8=Albert A.|last9=Young|first9=Sheila G.|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=http://www.sciencedirect.com/science/article/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref>

Increased in severe illness<ref name=":8">{{Cite journal|last=Hardcastle|first=Sharni Lee|last2=Brenu|first2=Ekua Weba|last3=Johnston|first3=Samantha|last4=Nguyen|first4=Thao|last5=Huth|first5=Teilah|last6=Ramos|first6=Sandra|last7=Staines|first7=Donald|last8=Marshall-Gradisnik|first8=Sonya|date=2015-09-05|title=Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615236/|journal=International Journal of Medical Sciences|volume=12|issue=10|pages=764–772|doi=10.7150/ijms.12399|issn=1449-1907|pmc=4615236|pmid=26516304}}</ref>

Increased with illness severity<ref name=":11">{{Cite journal|last=Montoya|first=Jose G.|last2=Holmes|first2=Tyson H.|last3=Anderson|first3=Jill N.|last4=Maecker|first4=Holden T.|last5=Rosenberg-Hasson|first5=Yael|last6=Valencia|first6=Ian J.|last7=Chu|first7=Lily|last8=Younger|first8=Jarred W.|last9=Tato|first9=Cristina M.|date=2017-08-22|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|pages=E7150–E7158|doi=10.1073/pnas.1710519114|issn=1091-6490|pmc=5576836|pmid=28760971}}</ref>

Increased in early illness<ref name="Hornig, 2015" />
|Decreased<ref name=":17">{{Cite journal|last=Neu|first=Daniel|last2=Mairesse|first2=Olivier|last3=Montana|first3=Xavier|last4=Gilson|first4=Medhi|last5=Corazza|first5=Francis|last6=Lefevre|first6=Nicolas|last7=Linkowski|first7=Paul|last8=Le Bon|first8=Olivier|last9=Verbanck|first9=Paul|date=2014-09-01|title=Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome|url=https://doi.org/10.1007/s00421-014-2910-1|journal=European Journal of Applied Physiology|language=en|volume=114|issue=9|pages=1841–1851|doi=10.1007/s00421-014-2910-1|issn=1439-6327}}</ref>Decreased IFN-γ/IL-10 ratio<ref name=":3">{{Cite journal|last=ter Wolbeek|first=Maike|last2=van Doornen|first2=Lorenz J. P.|last3=Kavelaars|first3=Annemieke|last4=van de Putte|first4=Elise M.|last5=Schedlowski|first5=Manfred|last6=Heijnen|first6=Cobi J.|date=2007-11-01|title=Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents|url=http://www.sciencedirect.com/science/article/pii/S0889159107000906|journal=Brain, Behavior, and Immunity|language=en|volume=21|issue=8|pages=1063–1074|doi=10.1016/j.bbi.2007.04.007|issn=0889-1591}}</ref>

Decreased secretion from MAIT cells<ref name=":18">{{Cite journal|last=Karhan|first=Ece|last2=Gunter|first2=Courtney L.|last3=Ravanmehr|first3=Vida|last4=Horne|first4=Meghan|last5=Kozhaya|first5=Lina|last6=Renzullo|first6=Stephanie|last7=Placek|first7=Lindsey|last8=George|first8=Joshy|last9=Robinson|first9=Peter N.|date=2019-12-26|title=Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.biorxiv.org/content/10.1101/2019.12.23.887505v1|journal=bioRxiv|language=en|pages=2019.12.23.887505|doi=10.1101/2019.12.23.887505}}</ref>
|-
|IFN-λ
|(''Interferon lambda'')

Type III interferon. Immunity response against early stages of viral infection.
|
|
|-
|'''[[Interleukin|Interleukins]]'''
|
|
|
|-
|[[Interleukin 1|IL-1]]
|(''Interleukin 1 subgroups: IL-1β, IL-1α'')

Regulates immune and inflammatory response. Acts as a major mediator in central fatigue pathways<ref>{{Cite journal|last=Yadlapati|first=Sujani|last2=Efthimiou|first2=Petros|date=2016|title=Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26140469/|journal=Modern Rheumatology|volume=26|issue=1|pages=3–8|doi=10.3109/14397595.2015.1069459|issn=1439-7609|pmid=26140469}}</ref>

Elevation of IL-1 in the brain contributes “sickness behavior".<ref>{{Cite journal|last=Roerink|first=Megan E.|last2=van der Schaaf|first2=Marieke E.|last3=Dinarello|first3=Charles A.|last4=Knoop|first4=Hans|last5=van der Meer|first5=Jos W. M.|date=2017-01-21|title=Interleukin-1 as a mediator of fatigue in disease: a narrative review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251329/|journal=Journal of Neuroinflammation|volume=14|doi=10.1186/s12974-017-0796-7|issn=1742-2094|pmc=5251329|pmid=28109186}}</ref>
|Increased IL-1α<ref>{{Cite journal|last=Linde|first=A.|last2=Andersson|first2=B.|last3=Svenson|first3=S. B.|last4=Ahrne|first4=H.|last5=Carlsson|first5=M.|last6=Forsberg|first6=P.|last7=Hugo|first7=H.|last8=Karstorp|first8=A.|last9=Lenkei|first9=R.|date=Jun 1992|title=Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1316417/|journal=The Journal of Infectious Diseases|volume=165|issue=6|pages=994–1000|doi=10.1093/infdis/165.6.994|issn=0022-1899|pmid=1316417}}</ref><ref name=":1">{{Cite journal|last=Patarca|first=R.|last2=Klimas|first2=N. G.|last3=Lugtendorf|first3=S.|last4=Antoni|first4=M.|last5=Fletcher|first5=M. A.|date=Jan 1994|title=Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression|url=https://pubmed.ncbi.nlm.nih.gov/8148443/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S147–153|doi=10.1093/clinids/18.supplement_1.s147|issn=1058-4838|pmid=8148443}}</ref><ref name=":4">{{Cite journal|last=Fletcher|first=Mary Ann|last2=Zeng|first2=Xiao Rong|last3=Barnes|first3=Zachary|last4=Levis|first4=Silvina|last5=Klimas|first5=Nancy G.|date=2009-11-12|title=Plasma cytokines in women with chronic fatigue syndrome|url=https://doi.org/10.1186/1479-5876-7-96|journal=Journal of Translational Medicine|language=en|volume=7|issue=1|pages=96|doi=10.1186/1479-5876-7-96|issn=1479-5876|pmc=PMC2779802|pmid=19909538}}</ref><ref name=":19">{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Kubera|first3=Marta|last4=Ringel|first4=Karl|date=2012-02-01|title=Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin|url=http://www.sciencedirect.com/science/article/pii/S0165032711005301|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=933–939|doi=10.1016/j.jad.2011.09.004|issn=0165-0327}}</ref>

Increased IL-1α in females<ref name=":20">{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://doi.org/10.1186/1471-2172-14-29|journal=BMC Immunology|language=en|volume=14|issue=1|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=PMC3698072|pmid=23800166}}</ref>

Increased IL-1β<ref name=":4" /><ref name=":21">{{Cite journal|last=Scully|first=Paul|last2=McKernan|first2=Declan P|last3=Keohane|first3=John|last4=Groeger|first4=David|last5=Shanahan|first5=Fergus|last6=Dinan|first6=Timothy G|last7=Quigley|first7=Eamonn MM|date=2010-10|title=Plasma Cytokine Profiles in Females With Irritable Bowel Syndrome and Extra-Intestinal Co-Morbidity|url=https://journals.lww.com/ajg/Abstract/2010/10000/Plasma_Cytokine_Profiles_in_Females_With_Irritable.20.aspx|journal=American Journal of Gastroenterology|language=en-US|volume=105|issue=10|pages=2235–2243|doi=10.1038/ajg.2010.159|issn=0002-9270}}</ref><ref name=":19" /><ref name=":22">{{Cite journal|last=Lattie|first=Emily G.|last2=Antoni|first2=Michael H.|last3=Fletcher|first3=Mary Ann|last4=Penedo|first4=Frank|last5=Czaja|first5=Sara|last6=Lopez|first6=Corina|last7=Perdomo|first7=Dolores|last8=Sala|first8=Andreina|last9=Nair|first9=Sankaran|date=2012-08-01|title=Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911200061X|journal=Brain, Behavior, and Immunity|language=en|volume=26|issue=6|pages=849–858|doi=10.1016/j.bbi.2012.02.008|issn=0889-1591}}</ref><ref name=":17" />

Increased IL-1β, proportional to poor sleep quality<ref name=":10">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Ironson|first5=Gail H.|last6=Wohlgemuth|first6=William|last7=Nunez|first7=Maria Vera|last8=Garcia|first8=Lina|last9=Czaja|first9=Sara J.|date=2017-02-15|title=Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women|url=https://pubmed.ncbi.nlm.nih.gov/28038892/|journal=Journal of Neuroimmunology|volume=303|pages=43–50|doi=10.1016/j.jneuroim.2016.12.008|issn=1872-8421|pmc=5258835|pmid=28038892}}</ref>

Increased IL-1α in early illness<ref name=":13">{{Cite journal|last=Russell|first=Lindsey|last2=Broderick|first2=Gordon|last3=Taylor|first3=Renee|last4=Fernandes|first4=Henrique|last5=Harvey|first5=Jeanna|last6=Barnes|first6=Zachary|last7=Smylie|first7=AnneLiese|last8=Collado|first8=Fanny|last9=Balbin|first9=Elizabeth G.|date=2016-03-10|title=Illness progression in chronic fatigue syndrome: a shifting immune baseline|url=https://doi.org/10.1186/s12865-016-0142-3|journal=BMC Immunology|language=en|volume=17|issue=1|pages=3|doi=10.1186/s12865-016-0142-3|issn=1471-2172|pmc=PMC4785654|pmid=26965484}}</ref><ref name="Hornig, 2015" />

Increased IL-1RA in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14">{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|language=en|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327}}</ref>
|Decreased IL-1β in severe illness<ref name=":8" />Decreased IL-1β<ref name=":9">{{Cite journal|last=Hornig|first=M.|last2=Gottschalk|first2=G.|last3=Peterson|first3=D. L.|last4=Knox|first4=K. K.|last5=Schultz|first5=A. F.|last6=Eddy|first6=M. L.|last7=Che|first7=X.|last8=Lipkin|first8=W. I.|date=Feb 2016|title=Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.nature.com/articles/mp201529/|journal=Molecular Psychiatry|language=en|volume=21|issue=2|pages=261–269|doi=10.1038/mp.2015.29|issn=1476-5578}}</ref>

Decreased IL-1α and IL-1RA in later illness<ref name="Hornig, 2015" />

Decreased in later illness<ref name=":13" />
|-
|[[Interleukin 2|IL-2]]
|(''Interleukin 2'')

Stimulates T-Cell growth, regulates immune system, controls cellular proliferation and differentiation
|Increased<ref>{{Cite journal|last=Cheney|first=P. R.|last2=Dorman|first2=S. E.|last3=Bell|first3=D. S.|date=1989-02-15|title=Interleukin-2 and the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/2783643/|journal=Annals of Internal Medicine|volume=110|issue=4|pages=321|doi=10.7326/0003-4819-110-4-321_1|issn=0003-4819|pmid=2783643}}</ref><ref name=":6" /><ref name=":0">{{Cite journal|last=Milrad|first=Sara F.|last2=Hall|first2=Daniel L.|last3=Jutagir|first3=Devika R.|last4=Lattie|first4=Emily G.|last5=Czaja|first5=Sara J.|last6=Perdomo|first6=Dolores M.|last7=Fletcher|first7=Mary Ann|last8=Klimas|first8=Nancy|last9=Antoni|first9=Michael H.|date=2018-09-01|title=Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model|url=http://www.sciencedirect.com/science/article/pii/S0167876017301629|journal=International Journal of Psychophysiology|series=The Psychophysiology of Stress and Adaptation: Models, Pathways, and Implications|language=en|volume=131|pages=124–130|doi=10.1016/j.ijpsycho.2017.09.009|issn=0167-8760}}</ref><ref name=":16" /><ref name=":7" />

Increased in males<ref name=":20" />

|Depressed response post-exercise (increased in controls)<ref name=":12">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=en|volume=8|issue=1|pages=2779|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|-
|IL-3
|(''Interleukin 3'')

Regulates blood-cell production
|
|
|-
|[[Interleukin 4|IL-4]]
|(''Interleukin 4'')

Induces naive [[Helper T cell|helper T cells]] to develop into [[Th2]] cells. Regulates immune system
|Increased in early illness<ref name="Hornig, 2015" />

Increased<ref name=":1" /><ref name=":4" /><ref name=":16" />

Increased with illness severity<ref name=":11" />

|Decreased in females<ref name=":20" />
|-
|IL-5
|(''Interleukin 5'')

Regulates eosinophils in the bone marrow
|Increased<ref name=":4" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" /><ref name=":16" />
|-
|[[Interleukin 6|IL-6]]
|(''Interleukin 6'')

Regulates immune system

An important inflammatory cytokine and HPA axis modulator. IL-6 also plays a role in other CFS symptoms including hyperalgesia, fatigue, sleep impairment, and depression. It has been reported that IL-6 induces excessive daytime sleepiness or disturbed non-refreshing sleep in patients with CFS, and that increased levels are associated with a decrease in sleep quality.<ref name=":23">{{Cite journal|last=Yang|first=Tiansong|last2=Yang|first2=Yan|last3=Wang|first3=Delong|last4=Li|first4=Chaoran|last5=Qu|first5=Yuanyuan|last6=Guo|first6=Jing|last7=Shi|first7=Tianyu|last8=Bo|first8=Wang|last9=Sun|first9=Zhongren|date=2019-06-28|title=The clinical value of cytokines in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/|journal=Journal of Translational Medicine|volume=17|doi=10.1186/s12967-019-1948-6|issn=1479-5876|pmc=6599310|pmid=31253154}}</ref>
|Increased<ref name=":4" /><ref name=":0" /><ref name=":22" /><ref name=":16" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":7" />

Increased sIL-6R<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" /><ref>{{Cite journal|last=Nas|first=K.|last2=Cevik|first2=R.|last3=Batum|first3=S.|last4=Sarac|first4=A. J.|last5=Acar|first5=S.|last6=Kalkanli|first6=S.|date=2011|title=Immunologic and psychosocial status in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/21585130/|journal=Bratislavske Lekarske Listy|volume=112|issue=4|pages=208–212|issn=0006-9248|pmid=21585130}}</ref>

Increased LIF with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in later illness<ref name=":13" />

|Decreased<ref name=":3" /><ref name=":9" /><ref name=":17" />

Decreased in moderate illness<ref name=":8" />

Decreased LIF<ref name=":9" />

Decreased in early illness<ref name=":13" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>

Depressed response to LIF post-exercise (increased in controls)<ref name=":12" />
|-
|[[Interleukin 7|IL-7]]
|(''Interleukin 7'')

Regulates adaptive immune system
|Increased with illness severity<ref name=":11" /><ref name=":8" />
|Decreased<ref name="Landi2015" />
|-
|[[Interleukin 8|IL-8]]
|(''Interleukin 8'')

Regulates inflammatory response
|Increased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Increased in severe illness<ref name=":8" /><ref name=":17" />

Increased in sudden onset illness<ref name=":2">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Weaver|first2=Shelley A.|last3=Tseng|first3=Chin-Lin|last4=Ottenweller|first4=John E.|date=2005-01-01|title=Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome|url=https://cvi.asm.org/content/12/1/52|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=12|issue=1|pages=52–55|doi=10.1128/CDLI.12.1.52-55.2005|issn=1071-412X|pmid=15642984}}</ref>

Increased in early illness<ref name=":13" />

Increased in later illness<ref name="Hornig, 2015" />

|Decreased<ref name=":4" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />

Decreased in later illness<ref name=":13" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|IL-9
|(''Interleukin 9'')

Promotes mast cell growth, stimulates cell proliferation and prevents apoptosis
|
|Decreased<ref name=":16" />
|-
|[[Interleukin 10|IL-10]]
|(''Interleukin 10'')

Regulates anti-inflammatory response and immune response to pathogens
|Increased<ref name=":5" /><ref>{{Cite journal|last=Nakamura|first=Toru|last2=Schwander|first2=Stephan K.|last3=Donnelly|first3=Robert|last4=Ortega|first4=Felix|last5=Togo|first5=Fumiharu|last6=Broderick|first6=Gordon|last7=Yamamoto|first7=Yoshiharu|last8=Cherniack|first8=Neil S.|last9=Rapoport|first9=David|date=2010-04-01|title=Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia|url=https://cvi.asm.org/content/17/4/582|journal=Clinical and Vaccine Immunology|language=en|volume=17|issue=4|pages=582–587|doi=10.1128/CVI.00379-09|issn=1556-6811|pmid=20181767}}</ref><ref name=":17" /><ref name=":16" /><ref>{{Cite journal|last=Russell|first=Alice|last2=Hepgul|first2=Nilay|last3=Nikkheslat|first3=Naghmeh|last4=Borsini|first4=Alessandra|last5=Zajkowska|first5=Zuzanna|last6=Moll|first6=Natalie|last7=Forton|first7=Daniel|last8=Agarwal|first8=Kosh|last9=Chalder|first9=Trudie|date=2019-2|title=Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/|journal=Psychoneuroendocrinology|volume=100|pages=276–285|doi=10.1016/j.psyneuen.2018.11.032|issn=0306-4530|pmc=6350004|pmid=30567628}}</ref>

Increased in abnormal spinal fluid patients<ref name=":2" />

Increased at baseline (measurement 1)<ref name=":6" />

Increased IL-10 and decreased IFN-γ/IL-10 ratio<ref name=":3" />

|Decreased<ref>{{Cite journal|last=Borish|first=Larry|last2=Schmaling|first2=Karen|last3=DiClementi|first3=Jeannie D.|last4=Streib|first4=Joanne|last5=Negri|first5=Julie|last6=Jones|first6=James F.|date=1998-08-01|title=Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables|url=http://www.sciencedirect.com/science/article/pii/S0091674998700909|journal=Journal of Allergy and Clinical Immunology|language=en|volume=102|issue=2|pages=222–230|doi=10.1016/S0091-6749(98)70090-9|issn=0091-6749}}</ref><ref name=":9" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2015/929720/|title=Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|last=Peterson|first=D.|last2=Brenu|first2=E. W.|date=2015-03-05|website=Mediators of Inflammation|language=en|access-date=2020-11-19|last3=Gottschalk|first3=G.|last4=Ramos|first4=S.|last5=Nguyen|first5=T.|last6=Staines|first6=D.|last7=Marshall-Gradisnik|first7=S.}}</ref>

Decreased at 6 months (measurement 2)<ref name=":6" />
|-
|IL-11
|(''Interleukin 11'')

Regulates inflammation. Inhibits tissue regeneration<ref>{{Cite journal|last=Cook|first=Stuart A.|last2=Schafer|first2=Sebastian|date=2020-01-27|title=Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation|url=https://www.annualreviews.org/doi/10.1146/annurev-med-041818-011649|journal=Annual Review of Medicine|language=en|volume=71|issue=1|pages=263–276|doi=10.1146/annurev-med-041818-011649|issn=0066-4219}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|IL-12
|(''Interleukin 12'')

Regulates Th1 response, as well as activated T-cells, NK cells, and CTLs<ref>{{Cite journal|last=Rus|first=Violeta|last2=Via|first2=Charles S.|date=2007-01-01|editor-last=Tsokos|editor-first=George C.|editor2-last=Gordon|editor2-first=Caroline|editor3-last=Smolen|editor3-first=Josef S.|title=Chapter 12 - Cytokines in Systemic Lupus Erythematosus|url=http://www.sciencedirect.com/science/article/pii/B9780323044349500178|language=en|location=Philadelphia|publisher=Mosby|pages=109–120|isbn=978-0-323-04434-9}}</ref>
|Increased<ref name=":4" />

Increased IL-12p70 with illness severity<ref name=":11" />

Increased IL-12p70<ref name=":7" />

Increased IL-12p75<ref name=":16" />

Increased IL-12p40 in early illness<ref name="Hornig, 2015" />

|Decreased IL-12B<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response to IL-12p40 post-exercise (increased in controls)<ref name=":12" />

Decreased IL-12p40<ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref>
|-
|IL-13
|(''Interleukin 13'')

Regulates immune response (B-cells and monocytes). Involved in Th2 inflammation.<ref>{{Cite journal|last=Marone|first=Giancarlo|last2=Granata|first2=Francescopaolo|last3=Pucino|first3=Valentina|last4=Pecoraro|first4=Antonio|last5=Heffler|first5=Enrico|last6=Loffredo|first6=Stefania|last7=Scadding|first7=Guy W.|last8=Varricchi|first8=Gilda|date=2019|title=The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma|url=https://www.frontiersin.org/articles/10.3389/fphar.2019.01387/full|journal=Frontiers in Pharmacology|language=English|volume=10|doi=10.3389/fphar.2019.01387|issn=1663-9812}}</ref>
|Increased<ref name=":16" />

Increased in early illness<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":4" />
|-
|IL-15
|(''Interleukin 15'')

Stimulates activity of cytotoxic CD8+ T-cells and NK cells<ref>{{Cite journal|last=Carrero|first=Rosa M. Santana|last2=Beceren-Braun|first2=Figen|last3=Rivas|first3=Sarai C.|last4=Hegde|first4=Shweta M.|last5=Gangadharan|first5=Achintyan|last6=Plote|first6=Devin|last7=Pham|first7=Gabriel|last8=Anthony|first8=Scott M.|last9=Schluns|first9=Kimberly S.|date=2019-01-08|title=IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses|url=https://www.pnas.org/content/116/2/599|journal=Proceedings of the National Academy of Sciences|language=en|volume=116|issue=2|pages=599–608|doi=10.1073/pnas.1814642116|issn=0027-8424|pmid=30587590}}</ref>
|
|Decreased<ref name=":4" />
|-
|[[Interleukin 16|IL-16]]
|''(Interleukin 16)''

Modulates T-cell activation
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[Interleukin 17|IL-17]]
|(''Interleukin 17'')

IL-17A and IL-17F regulate immune and inflammatory response in local tissue infection
|Increased IL-17F with illness severity<ref name=":11" />

Increased IL-17A in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":6" />

Decreased IL-17F<ref name=":9" /><ref name=":16" />

Decreased IL-17A in later illness<ref name="Hornig, 2015" />

Depressed response to IL-17F post-exercise (increased in controls)<ref name=":12" />

Decreased secretion from CCR6+ Th17 cells and MAIT cells<ref name=":18" />
|-
|IL-23
|''(Interleukin 23)''

Regulates inflammatory autoimmune responses
|Increased in males<ref name=":20" />

|Decreased<ref>{{Cite journal|last=Broderick|first=Gordon|last2=Katz|first2=Ben Z.|last3=Fernandes|first3=Henrique|last4=Fletcher|first4=Mary Ann|last5=Klimas|first5=Nancy|last6=Smith|first6=Frederick A.|last7=O’Gorman|first7=Maurice RG|last8=Vernon|first8=Suzanne D.|last9=Taylor|first9=Renee|date=2012-09-13|title=Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue|url=https://doi.org/10.1186/1479-5876-10-191|journal=Journal of Translational Medicine|language=en|volume=10|issue=1|pages=191|doi=10.1186/1479-5876-10-191|issn=1479-5876|pmc=PMC3480896|pmid=22973830}}</ref>

Decreased IL-23p40<ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref>
|-
|[[Tumor necrosis factor|'''Tumor Necrosis Factor''']]
|
|
|
|-
|[[TNF-alpha|TNF-α]]
|(''Tumor Necrosis Factor alpha'')

Regulates acute and chronic inflammation<ref>{{Cite web|url=https://www.hindawi.com/journals/tswj/2013/875363/|title=The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease|last=Galeone|first=Antonella|last2=Paparella|first2=Domenico|date=2013-11-06|website=The Scientific World Journal|language=en|access-date=2020-11-20|last3=Colucci|first3=Silvia|last4=Grano|first4=Maria|last5=Brunetti|first5=Giacomina}}</ref>
|Increased<ref name=":5" /><ref name=":0" /><ref name=":21" /><ref name=":19" /><ref name=":17" /><ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref><ref name=":6" />

Increased post-exercise<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref>

Increased TNF-α and sTNFR1<ref name=":1" />

Increased, proportional to poor sleep quality<ref name=":10" />

Increased in early illness<ref name="Hornig, 2015" />

Increased in those with 5-HT autoimmune activity<ref name=":14" />

|Decreased<ref name=":3" />

Decreased in later illness<ref name="Hornig, 2015" />

Depressed response post-exercise (increased in controls)<ref name=":12" /><ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02079.x|journal=Journal of Internal Medicine|language=en|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796}}</ref>
|-
|[[Lymphotoxin-alpha|LT-α]]
|(''Lymphotoxin alpha - formerly TNF-β tumor necrosis factor-beta'')

Regulates innate immune response
|Increased<ref name=":1" /><ref name=":4" />

|Decreased<ref name=":3" /><ref name=":9" />

Decreased post-exercise<ref name=":12" />
|-
|FasL
|(''Fas ligand or CD95L or CD178'')

Regulates immune response and apoptosis
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|TNFSF10
|(''TNF superfamily member 10 or TRAIL'')

Regulates apoptosis in transformed cells and mostly functional in immune cells<ref>{{Cite journal|last=Tayyeb|first=Asima|last2=Shah|first2=Zafar Abbas|date=2019-07-02|title=Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma|url=https://www.heighpubs.org/hjcsr/acst-aid1005.php|journal=Archives of Cancer Science and Therapy|language=en|volume=3|issue=1|pages=025–034|doi=10.29328/journal.acst.1001005}}</ref>
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />
|-
|CD40L
|(''CD40 ligand or CD154'')

Regulates immune response
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased in early illness<ref name="Hornig, 2015" />

Decreased<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8986.2010.00978.x|journal=Psychophysiology|language=en|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1469-8986|pmc=PMC4378647|pmid=20230500}}</ref>
|-
|'''[[Chemokine|Chemokines]]'''
|
|
|
|-
|[[CCL2]]
|(''C-C motif chemokine ligand 2'')

Regulates inflammatory response
|Increased in early illness<ref name="Hornig, 2015" />

|Decreased in later illness<ref name="Hornig, 2015" />

No change post-exercise, yet change in controls<ref name=":12" />
|-
|[[CCL4]]
|(''C-C motif chemokine ligand 4 or MIP-1β'')

Regulates inflammatory response
|
|Decreased post-exercise<ref name=":12" />
|-
|[[CCL5]]
|''(C-C motif chemokine ligand 5 or RANTES regulated on activation, normal T cell expressed and secreted'')

Regulates inflammatory response
|Increased in moderate illness<ref name=":8" />
|
|-
|[[CCL11]]
|(''C-C motif chemokine ligand 11)''

Regulates inflammatory response
|Increased<ref name=":9" />

Increased with illness severity<ref name=":11" />
|
|-
|CCL24
|(''C-C motif chemokine ligand 24)''
|Increased in later illness<ref name="Landi2015" />
|
|-
|[[CXCL1]]
|(''C-X-C motif chemokine ligand 1'')

Regulates immune response via neutrophils<ref>{{Cite journal|last=Sawant|first=Kirti V.|last2=Poluri|first2=Krishna Mohan|last3=Dutta|first3=Amit K.|last4=Sepuru|first4=Krishna Mohan|last5=Troshkina|first5=Anna|last6=Garofalo|first6=Roberto P.|last7=Rajarathnam|first7=Krishna|date=2016-09-14|title=Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions|url=https://www.nature.com/articles/srep33123|journal=Scientific Reports|language=en|volume=6|issue=1|pages=33123|doi=10.1038/srep33123|issn=2045-2322}}</ref>
|Increased with illness severity<ref name=":11" />
|
|-
|CX3CL1
|(''C-X3-C motif chemokine ligand 1'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[CXCL9]]
|(''C-X-C motif chemokine ligand 9'')
|
|Decreased in later illness<ref name="Landi2015" />
|-
|[[IP-10|CXCL10]]
|(''C-X-C motif chemokine ligand 10 or IP-10'')

Regulates immune response via T cells, eosinophils, monocytes and NK cells<ref>{{Cite journal|last=Vazirinejad|first=Reza|last2=Ahmadi|first2=Zahra|last3=Arababadi|first3=Mohammad Kazemi|last4=Hassanshahi|first4=Gholamhossein|last5=Kennedy|first5=Derek|date=2014|title=The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis|url=https://www.karger.com/Article/FullText/357780|journal=Neuroimmunomodulation|language=english|volume=21|issue=6|pages=322–330|doi=10.1159/000357780|issn=1021-7401|pmid=24642726}}</ref>
|Increased<ref name=":9" /><ref name=":7" />

Increased with illness severity<ref name=":11" />

Increased post-exercise<ref name=":12" />

|Decreased<ref>{{Cite web|url=https://www.hindawi.com/journals/mi/2018/3972104/|title=Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome|last=Lynn|first=Megan|last2=Maclachlan|first2=Laura|date=2018-06-10|website=Mediators of Inflammation|language=en|access-date=2020-11-21|last3=Finkelmeyer|first3=Andreas|last4=Clark|first4=James|last5=Locke|first5=James|last6=Todryk|first6=Stephen|last7=Ng|first7=Wan-Fai|last8=Newton|first8=Julia L.|last9=Watson|first9=Stuart}}</ref>
|-
|'''Colon Stimulating Factors'''
|
|
|
|-
|CSF1
|''(Colony stimulating factor 1 or M-CSF macrophage colony-stimulating factor)''

Regulates innate immunity and inflammatory response. Controls cellular proliferation and differentiation of monocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF1|title=CSF1 Gene - GeneCards {{!}} CSF1 Protein {{!}} CSF1 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />
|-
|CSF2
|''(Colony stimulating factor 2 or GM-CSF granulocyte-macrophage colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes and macrophages<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF2|title=CSF2 Gene - GeneCards {{!}} CSF2 Protein {{!}} CSF2 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased<ref name=":7" />

Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|CSF3
|''(Colony stimulating factor 3 or G-CSF granulocyte colony-stimulating factor)''

Controls cellular proliferation and differentiation of granulocytes<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSF3|title=CSF3 Gene - GeneCards {{!}} CSF3 Protein {{!}} CSF3 Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|Increased with illness severity<ref name=":11" />

|Decreased<ref name=":9" />
|-
|KITLG
|''(KIT ligand or SCF stem cell factor or MCGF mast cell growth factor or SLF steel factor)''

Regulates cell survival and proliferation
|Increased with illness severity<ref name=":11" />

Increased in early illness<ref name="Hornig, 2015" />

|Decreased<ref name=":9" />

Decreased in later illness<ref name="Hornig, 2015" />
|-
|'''Transforming Growth Factors'''
|
|
|
|-
|TGF-α
|''(Transforming growth factor alpha)''

Regulates cellular proliferation and differentiation
|Increased with illness severity<ref name=":11" />
|
|-
|[[Transforming growth factor beta|TGF‐β]]
|''(Transforming growth factor beta)''

Regulates cellular proliferation and differentiation, and inflammatory processes
|Increased<ref name=":11" /><ref>{{Cite journal|last=Chao|first=Chun C.|last2=Janoff|first2=Edward N.|last3=Hu|first3=Shuxian|last4=Thomas|first4=Kelly|last5=Gallagher|first5=Michael|last6=Tsang|first6=Monica|last7=Peterson|first7=Phillip K.|date=1991-07-01|title=Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/1043466691904972|journal=Cytokine|language=en|volume=3|issue=4|pages=292–298|doi=10.1016/1043-4666(91)90497-2|issn=1043-4666}}</ref><ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=1994-03-01|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

Increased TGF-β1<ref>{{Cite journal|last=White|first=P. D.|last2=Nye|first2=K. E.|last3=Pinching|first3=A. J.|last4=Yap|first4=T. M.|last5=Power|first5=N.|last6=Vleck|first6=V.|last7=Bentley|first7=D. J.|last8=Thomas|first8=J. M.|last9=Buckland|first9=M.|date=2004-01-01|title=Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v12n02_06|journal=Journal of Chronic Fatigue Syndrome|volume=12|issue=2|pages=51–66|doi=10.1300/J092v12n02_06|issn=1057-3321}}</ref><ref>{{Cite journal|last=Kennedy|first=G.|last2=Spence|first2=V.|last3=Underwood|first3=C.|last4=Belch|first4=J. J. F.|date=2004-08-01|title=Increased neutrophil apoptosis in chronic fatigue syndrome|url=https://jcp.bmj.com/content/57/8/891|journal=Journal of Clinical Pathology|language=en|volume=57|issue=8|pages=891–893|doi=10.1136/jcp.2003.015511|issn=0021-9746|pmid=15280416}}</ref>

Increased at rest, but not post-exercise<ref>{{Cite journal|last=Clark|first=L. V.|last2=Buckland|first2=M.|last3=Murphy|first3=G.|last4=Taylor|first4=N.|last5=Vleck|first5=V.|last6=Mein|first6=C.|last7=Wozniak|first7=E.|last8=Smuk|first8=M.|last9=White|first9=P. D.|date=2017|title=Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13023|journal=Clinical & Experimental Immunology|language=en|volume=190|issue=3|pages=360–371|doi=10.1111/cei.13023|issn=1365-2249|pmc=PMC5680051|pmid=28779554}}</ref>
|
|-
|Activin
|Part of the TGF-β protein superfamily. Involved in the control of inflammation and muscle mass<ref name=":15">{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Lewis|first3=Donald P.|last4=Hayward|first4=Susan|last5=Ludlow|first5=Helen|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|date=2017-03-16|title=Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study|url=https://doi.org/10.1186/s12967-017-1161-4|journal=Journal of Translational Medicine|volume=15|issue=1|pages=60|doi=10.1186/s12967-017-1161-4|issn=1479-5876|pmc=PMC5353946|pmid=28302133}}</ref>
|Increased Activin B<ref>{{Cite journal|last=Richardson|first=Alice M.|last2=Lewis|first2=Don P.|last3=Kita|first3=Badia|last4=Ludlow|first4=Helen|last5=Groome|first5=Nigel P.|last6=Hedger|first6=Mark P.|last7=de Kretser|first7=David M.|last8=Lidbury|first8=Brett A.|date=2018-04-12|title=Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection|url=https://doi.org/10.1186/s12967-018-1473-z|journal=Journal of Translational Medicine|volume=16|issue=1|pages=97|doi=10.1186/s12967-018-1473-z|issn=1479-5876|pmc=PMC5898049|pmid=29650052}}</ref><ref name=":15" />
|Decreased Activin B<ref>{{Cite journal|last=Lidbury|first=Brett A.|last2=Kita|first2=Badia|last3=Richardson|first3=Alice M.|last4=Lewis|first4=Donald P.|last5=Privitera|first5=Edwina|last6=Hayward|first6=Susan|last7=de Kretser|first7=David|last8=Hedger|first8=Mark|date=2019-07-19|title=Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity|url=https://pubmed.ncbi.nlm.nih.gov/31331036/|journal=Diagnostics (Basel, Switzerland)|volume=9|issue=3|doi=10.3390/diagnostics9030079|issn=2075-4418|pmc=6787626|pmid=31331036}}</ref>
|-
|[[Growth differentiation factor 15|GDF15]]
|''(Growth differentiation factor 15)''

Part of the TGF-β protein superfamily. Highly elevated GDF15 has been linked to mitochondrial disorders and skeletal muscle fatigue<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|Increased<ref>{{Cite journal|last=Melvin|first=A.|last2=Lacerda|first2=E.|last3=Dockrell|first3=H. M.|last4=O’Rahilly|first4=S.|last5=Nacul|first5=L.|date=2019-12-04|title=Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://doi.org/10.1186/s12967-019-02153-6|journal=Journal of Translational Medicine|volume=17|issue=1|pages=409|doi=10.1186/s12967-019-02153-6|issn=1479-5876|pmc=PMC6892232|pmid=31801546}}</ref>
|
|-
|'''Adipokines'''
|
|
|
|-
|[[Leptin]]
|Dual role, acting as both a hormone and cytokine. Critical in metabolic function. Helps regulate innate and adaptive immune response<ref>{{Cite journal|last=La Cava|first=Antonio|date=2017-10|title=Leptin in inflammation and autoimmunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453851/|journal=Cytokine|volume=98|pages=51–58|doi=10.1016/j.cyto.2016.10.011|issn=1043-4666|pmc=5453851|pmid=27916613}}</ref>
|Increased<ref name="Hornig, 2015" />

Increased with illness severity<ref name=":11" /><ref>{{Cite journal|last=Stringer|first=Elizabeth Ann|last2=Baker|first2=Katharine Susanne|last3=Carroll|first3=Ian R.|last4=Montoya|first4=Jose G.|last5=Chu|first5=Lily|last6=Maecker|first6=Holden T.|last7=Younger|first7=Jarred W.|date=2013-04-09|title=Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology|url=https://doi.org/10.1186/1479-5876-11-93|journal=Journal of Translational Medicine|language=en|volume=11|issue=1|pages=93|doi=10.1186/1479-5876-11-93|issn=1479-5876|pmc=PMC3637529|pmid=23570606}}</ref>
|
|-
|Resistin
|''(Also known as ADSF adipose tissue-specific secretory factor or XCP1 C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein)''
|
|Decreased<ref name=":11" />
|-
|'''Neurotrophins'''
|
|
|
|-
|NGF
|''(Nerve growth factor)''

Regulates neuronal cell function and immune cell activity<ref>{{Cite journal|last=Minnone|first=Gaetana|last2=De Benedetti|first2=Fabrizio|last3=Bracci-Laudiero|first3=Luisa|date=2017-05-11|title=NGF and Its Receptors in the Regulation of Inflammatory Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454940/|journal=International Journal of Molecular Sciences|volume=18|issue=5|doi=10.3390/ijms18051028|issn=1422-0067|pmc=5454940|pmid=28492466}}</ref>
|Increased with illness severity<ref name=":11" /><ref>{{Cite journal|date=2020-03-01|title=The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms|url=https://www.sciencedirect.com/science/article/pii/S0306453019313198|journal=Psychoneuroendocrinology|language=en|volume=113|pages=104578|doi=10.1016/j.psyneuen.2019.104578|issn=0306-4530}}</ref>
|
|-
|'''Other Growth Factors'''
|
|
|
|-
|PDGFB
|''(Platelet derived growth factor subunit B)''

Regulates cellular proliferation and differentiation, and embryonic development<ref>{{Cite web|url=https://medlineplus.gov/genetics/gene/pdgfb/|title=PDGFB gene: MedlinePlus Genetics|website=medlineplus.gov|language=en|access-date=2020-11-20}}</ref>
|Increased in later illness<ref name="Hornig, 2015" />

|Decreased PDGF-BB<ref name=":9" />

Decreased in early illness<ref name="Hornig, 2015" />
|-
|FGF2
|''(Fibroblast growth factor 2 or bFGF basic fibroblast growth factor or FGF-β)''

Regulates cellular proliferation and differentiation
|
|Decreased<ref name=":9" />
|-
|[[Vascular endothelial growth factor|VEGFA]]
|''(Vascular endothelial growth factor A)''

Regulates cellular proliferation and differentiation of vascular endothelial cells<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=VEGFA|title=VEGFA Gene - GeneCards {{!}} VEGFA Protein {{!}} VEGFA Antibody|website=www.genecards.org|access-date=2020-11-20}}</ref>
|
|Decreased<ref name=":9" />

Decreased in later illness<ref name="Landi2015" />
|}

== Cytokines and Chemokines ==
Chemokines are cytokines that induce chemotaxis. Chemotaxis is the orchestrated movement of cells towards a specific location flagged by a chemical messenger. Unlike cytokines, chemokines have just one major role: to direct leukocytes toward pathogens, or to areas of injured/diseased tissue.
*[http://www.wisegeek.org/what-is-the-difference-between-a-cytokine-and-a-chemokine.htm What is the Difference Between a Cytokine and a Chemokine?] (WiseGEEK)

==Notable studies==
*2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Broderick|first=Gordon|author-link=Gordon Broderick|last2=Fuite|first2=Jim|author-link2=Jim Fuite|last3=Kreitz|first3=Andrea|author-link3=Andrea Kreitz|last4=Vernon|first4=Suzanne D|author-link4=Suzanne Vernon|last5=Klimas|first5=Nancy|author-link5=Nancy Klimas|last6=Fletcher|first6=Mary Ann|author-link6=Mary Ann Fletcher|date=Oct 2010|title=A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/|journal=[[Brain, behavior, and immunity]]|volume=24|issue=7|pages=1209–1217|doi=10.1016/j.bbi.2010.04.012|issn=0889-1591|pmc=2939140|pmid=20447453|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939140/ (Full text)]
*2015, [http://advances.sciencemag.org/content/1/1/e1400121 Distinct plasma immune signatures in ME/CFS are present early in the course of illness]<ref name="Hornig, 2015" />
*2015, [http://www.sciencedirect.com/science/article/pii/S088915911400614X Plasma cytokine expression in adolescent chronic fatigue syndrome]<ref name="Wyller, 2016" />
*2016, [http://www.sciencedirect.com/science/article/pii/S1043466615301071 Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Landi2015">{{Cite journal|last=Landi|first=Abdolamir|author-link=Amir Landi|last2=Broadhurst|first2=David|author-link2=|last3=Vernon|first3=Suzanne D.|author-link3=Suzanne Vernon|last4=Tyrrell|first4=D. Lorne J.|author-link4=|last5=Houghton|first5=Michael|author-link5=Michael Houghton|date=Feb 2016|title=Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1043466615301071|journal=Cytokine|language=en|volume=78|issue=|pages=27–36|doi=10.1016/j.cyto.2015.11.018|quote=|via=}}</ref>
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name=":11" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full text)]
*2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment<ref>Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and [[Jos van der Meer|Jos W. M. van der Meer]], Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment, Journal of Translational Medicine, 2017 Vol 15:267 https://doi.org/10.1186/s12967-017-1371-9</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9 (Full text)]
*2019, The clinical value of cytokines in chronic fatigue syndrome<ref name=":23" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599310/ (Full text)]

== Learn More ==
* [https://www.genenames.org/ HGNC - Official nomenclature for cytokines, chemokines, and growth factors]

==See also==

*[[Diagnostic biomarker]]

== References ==
<references>
<ref name="Hornig, 2015">{{Citation
| last1 = Hornig | first1 = M | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = JG | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = NG | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = SM | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = D | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = L | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = DL | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = CG | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = AF | authorlink9 = Andrew Schultz
| last10 = Che | first10 = X | authorlink10 = Xiaoyu Che
| last11 = Eddy | first11 = ML | authorlink11 = Meredith Eddy
| last12 = Komaroff | first12 = AL | authorlink12 = Anthony Komaroff
| last13 = Lipkin | first13 = WI | authorlink13 = Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1 | page =
| date = 2015
| pmid =
| doi = 10.1126/sciadv.1400121
| url = http://advances.sciencemag.org/content/1/1/e1400121.full
}}
</ref>
<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 = Tyson Holmes
| last3 = Anderson | first3 = Jill N. | authorlink3 = Jill Anderson
| last4 = Maecker | first4 = Holden T. | authorlink4 = Holden Maecker
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = Yael Rosenberg-Hasson
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 = Cristina Tato
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}
</ref>
<ref name="Wyller, 2016">{{Citation
| last1 = Wyller | first1 = Vegard Bruun | authorlink1 = Vegard Wyller
| last2 = Sørensend | first2 = Øystein | authorlink2 = Øystein Sørensend
| last3 = Sulheima | first3 = Dag | authorlink3 = Dag Sulheima
| last4 = Fagermoen | first4 = Even | authorlink4 = Even Fagermoen
| last5 = Ueland | first5 = Thor | authorlink5 = Thor Ueland
| last6 = Mollnes | first6 = Tom Eirik | authorlink6 = Tom Mollnes
| title = Plasma cytokine expression in adolescent chronic fatigue syndrome
| journal = Brain, Behavior, and Immunity | volume = 46 | issue = | page = 80–86
| date = 2015
| pmid =
| doi = 10.1016/j.bbi.2014.12.025
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Immunology]]