There are many different cytokines. They function as messenger molecules passing information around the body. They resemble hormones in this way, but they are usually communicating in response to something external and lead to inflammatory or immune responses.
Types of cytokines[edit | edit source]
Cellular immune response[edit | edit source]
Antibody response[edit | edit source]
Role in human disease[edit | edit source]
Chronic Fatigue Syndrome[edit | edit source]
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. In 2017, a 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."
Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al).  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."
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[edit | edit source]
Fibromyalgia: Cytokines IL-1beta, IL-6 and TNF-alpha are involved with central and peripheral neuropathic pain which is experienced by Fibromyalgia patients. Profiles are distinguishing Lupus and Rheumatoid Arthritis from Fibromyalgia.
Table of Cytokines[edit | edit source]
|Interferons||Interferons are antiviral agents that modulate the immune system. They stimulate Natural killer cells and macrophages to elicit antiviral and anti-tumor responses.|
|Interferon Type 1||Produced when the body recognizes a virus has invaded it.|
|IFN-α||Produced by Leucocytes.|
|IFN-β||Is produced in fibroblasts by RNAseL. It is used to reduce relapses in relapsing-remitting multiple sclerosis.|
|Interferon Type II|
|IFN-γ||The only Type II interferon in humans, it is produced by T cells and natural killer cells. It has weak anti-viral and anti-tumor effects but potentiates the effects of Type I interferons.||Elevated||Elevated in early illness.|
|Interferon Type III|
|IL-1||Elevated in early illness, reduced in later illness.|
|IL-4||Induces naive helper T cells to develop into Th2 cells.||Elevated||Elevated in early illness.|
|IL-6||Elevated||Russel found lower in early illness, higher for subjects ill for more than 2 years and over 18 years of age. Hornig found the reverse.|
|IL-8||Russel found higher in the recently afflicted, lower for subjects ill for more than 2 years. Hornig found the reverse.|
|IL-11||Elevated in early illness, reduced in later illness.|
|IL-13||Elevated||Elevated in early illness.|
|IL-17||Elevated in early illness, reduced in later illness.|
|Tumor Necrosis Factor|
Cytokines and Chemokines[edit | edit source]
Notable studies[edit | edit source]
- 2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome - (Full text)
- 2015, Distinct plasma immune signatures in ME/CFS are present early in the course of illness
- 2015, Plasma cytokine expression in adolescent chronic fatigue syndrome
- 2016, Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome
- 2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients - (Full text)
- 2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment - (Full text)
- 2019, The clinical value of cytokines in chronic fatigue syndrome - (Full text)
See also[edit | edit source]
References[edit | edit source]
- Merriam-Webster Medical Dictionary. "Definition of CYTOKINE". www.merriam-webster.com. Retrieved Oct 6, 2018.
- Hornig, M; Montoya, JG; Klimas, NG; Levine, SM; Felsenstein, D; Bateman, L; Peterson, DL; Gottschalk, CG; Schultz, AF; Che, X; Eddy, ML; Komaroff, AL; Lipkin, WI (2015), "Distinct plasma immune signatures in ME/CFS are present early in the course of illness", Science Advances, 1 (1), doi:10.1126/sciadv.1400121
- Montoya, Jose G.; Holmes, Tyson H.; Anderson, Jill N.; Maecker, Holden T.; Rosenberg-Hasson, Yael; Valencia, Ian J.; Chu, Lily; Younger, Jarred W.; Tato, Cristina M.; Davis, Mark M. (2017), "Cytokine signature associated with disease severity in chronic fatigue syndrome patients", Proceedings of the National Academy of Sciences of the United States of America, 114 (34): E7150-E7158, doi:10.1073/pnas.1710519114
- Landi, Abdolamir; Broadhurst, David; Vernon, Suzanne D.; Tyrrell, D. Lorne J.; Houghton, Michael (Feb 2016). "Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome". Cytokine. 78: 27–36. doi:10.1016/j.cyto.2015.11.018.
- Lipkin, W. I.; Peterson, D. L.; Ukaigwe, J. E.; Che, X.; Eddy, M. L.; Gottschalk, C. G.; Hornig, M. (Apr 2017). "Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations". Translational Psychiatry. 7 (4): e1080. doi:10.1038/tp.2017.44. ISSN 2158-3188.
- Staud, Roland (Mar 2004). "Fibromyalgia pain: do we know the source?". Current Opinion in Rheumatology. 16 (2): 157–163. ISSN 1040-8711. PMID 14770104.
- Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM
- Russell, Lindsey (Mar 10, 2016). "Illness progression in chronic fatigue syndrome: a shifting immune baseline". BMC Immunology.
- Broderick, Gordon; Fuite, Jim; Kreitz, Andrea; Vernon, Suzanne D; Klimas, Nancy; Fletcher, Mary Ann (Oct 2010). "A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome". Brain, behavior, and immunity. 24 (7): 1209–1217. doi:10.1016/j.bbi.2010.04.012. ISSN 0889-1591. PMC . PMID 20447453.
- Wyller, Vegard Bruun; Sørensend, Øystein; Sulheima, Dag; Fagermoen, Even; Ueland, Thor; Mollnes, Tom Eirik (2015), "Plasma cytokine expression in adolescent chronic fatigue syndrome", Brain, Behavior, and Immunity, 46: 80–86, doi:10.1016/j.bbi.2014.12.025
- Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and 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
- Yang, Tiansong; Yang, Yan; Wang, Delong; Li, Chaoran; Qu, Yuanyuan; Guo, Jing; Shi, Tianyu; Bo, Wang; Sun, Zhongren (Dec 2019). "The clinical value of cytokines in chronic fatigue syndrome". Journal of Translational Medicine. 17 (1). doi:10.1186/s12967-019-1948-6. ISSN 1479-5876. PMID 31253154.
Antibody - Antibodies or immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.
Myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.
Accuracy - The "closeness of an observation to the true clinical state". With respect to diagnostic tests, "accuracy" means how specific and sensitive the test is.