Cytokine

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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 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]

IFN-γ, TNFα

Antibody response[edit | edit source]

TGF-β, IL-4, IL-10, IL-13

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. [1] 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."[2]

Two large 2015 studies found a general pattern of down regulation in long term patients (Hornig, et al and Landi, et al). [3] 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."[4]

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. (A search of http://www.medscape.com/viewarticle/470556_8 may be necessary to view article or a Medscape login.)[5] Profiles are distinguishing Lupus and Rheumatoid Arthritis from Fibromyalgia.[6]

Table of Cytokines[edit | edit source]

Cytokine Description Th1 Th2 ME/CFS Fibromyalgia POTS
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.
IFN-κ
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.[7]
Interferon Type III
IFN-λ
Interleukins
IL-1 Elevated in early illness, reduced in later illness.[8]
IL-2 Elevated
IL-3
IL-4 Induces naive helper T cells to develop into Th2 cells. Elevated Elevated in early illness.[8]
IL-5 Elevated
IL-6 Elevated Russel found lower in early illness, higher for subjects ill for more than 2 years and over 18 years of age.[9] Hornig found the reverse.[8]
IL-7
IL-8 Russel found higher in the recently afflicted, lower for subjects ill for more than 2 years.[9] Hornig found the reverse.[8]
IL-9 Elevated
IL-10 Elevated
IL-11 Elevated in early illness, reduced in later illness.[8]
IL-12
IL-13 Elevated Elevated in early illness.[8]
IL-15
IL-17 Elevated in early illness, reduced in later illness.[8]
Tumor Necrosis Factor
TNF-alpha ElevatedTemplate:Fix/category[citation needed]
TNF-beta Elevated
Chemokines

Cytokines and Chemokines[edit | edit source]

Notable Studies[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Distinct plasma immune signatures - Science Advances
  2. 2.0 2.1 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 
  3. Study finds evidence of downregulated immune system in ME/CFS patients - MEAtcion - Landi, et al.
  4. New Research Discovers Evidence of Atypical & Classical ME/CFS - The Microbe Discovery Project - Apr 4, 2017
  5. Role of Cytokines for Fibromyalgia Syndrome Pain - Fibromyalgia Pain: Do We Know the Source - Medscape By: Roland Staud
  6. Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM
  7. Hornig, Mady (February 27, 2015). "Distinct plasma immune signatures in ME/CFS are present early in the course of illness". Science Advances. 
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 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 
  9. 9.0 9.1 Russell, Lindsey (March 10, 2016). "Illness progression in chronic fatigue syndrome: a shifting immune baseline". BMC Immunology. 
  10. 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 
  11. Landi, Abdolamir; Broadhurst, David; Vernon, Suzanne D; Tyrrell, D. Lorne J.; Houghton, Michael (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, PMID 26615570 
  12. 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


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From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history