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]
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. (A search of http://www.medscape.com/viewarticle/470556_8 may be necessary to view article or a Medscape login.) Profiles are distinguishing Lupus and Rheumatoid Arthritis from Fibromyalgia.
Cytokines and Chemokines[edit | edit source]
Notable Studies[edit | edit source]
- 2017, Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment (FULL TEXT)
- 2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients (FULL TEXT)
- 2016, Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome
ABSTRACT: "Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients...In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes...
- 2015, Distinct plasma immune signatures in ME/CFS are present early in the course of illness
"Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS."
- 2015, Plasma cytokine expression in adolescent chronic fatigue syndrome
"Highlights: Chronic fatigue syndrome (CFS) might be related to altered cytokine expression. A total of 120 adolescent CFS patients and 68 healthy controls were studied. Individual cytokine levels where similar across the two groups. Cytokine network parameters (ARACNE algorithm) were similar across the two groups. In CFS patients, there were no associations between symptoms and network parameters."
See also[edit | edit source]
References[edit | edit source]
- Distinct plasma immune signatures - Science Advances
- 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
- Study finds evidence of downregulated immune system in ME/CFS patients - MEAtcion - Landi, et al.
- New Research Discovers Evidence of Atypical & Classical ME/CFS - The Microbe Discovery Project - Apr 4, 2017
- Role of Cytokines for Fibromyalgia Syndrome Pain - Fibromyalgia Pain: Do We Know the Source - Medscape By: Roland Staud
- Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. PubMed.gov NCBI-NLM
- 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
- 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
- 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
- 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