Patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) were shown to have a differential cytokine signature compared with healthy controls, with overall differences in the levels of 2 cytokines and severity-dependent differences for 17 cytokines, according to a recent study published in PNAS.1

In this case control study, researchers recruited age- and sex-matched patients with ME/CFS (n=192) and healthy controls (n=392). Cytokine signatures were determined with a 51-multiplex array and were regressed based on ME/CFS severity and fatigue duration. Results were adjusted for age, race, sex, and nonspecific binding.

Among patients with ME/CFS, researchers found that the levels of TGF- were higher (P=.005) and resistin levels were lower (P=.005) compared with healthy controls. 

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When cytokines were evaluated in relation to disease severity, 17 cytokines were positively correlated with ME/CFS severity: eotaxin-1 (CCL11), CXCL1 (GROα), CXCL10 (IP-10), interferon-γ, interleukin (IL)-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. A total of 13 of these cytokines are proinflammatory. The study authors suggested that this may contribute to the immunopathology and symptoms of ME/CFS.

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After adjusting the data for covariates, CXCL9 (MIG) was inversely correlated with fatigue duration.

The researchers concluded that “findings in this study provide further evidence that ME/CFS likely involves a systemic inflammatory process,” and suggest that their findings “also support biological plausibility for the propensity of these patients to experience several major and ongoing clinical manifestations… and support the suitability of exploring immunomodulation as a primary or adjuvant therapy.”


  1. Montoya JG, Holmes TH, Anderson JN, et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci USA. 2017;114:E7150-E7158.