Cytokine Concentration Linked to Chronic Fatigue Syndrome

More than one million people in the USA suffer from chronic fatigue syndrome, also known as myalgic encephomyelitis and designated by the acronym ME/CFS. It is a disease with no known cure or even reliably effective treatments.

Three of every four ME/CFS patients are women, for reasons that are not understood. It characteristically arises in two major waves: among adolescents between the ages of 15 and 20, and in adults between 30 and 35. The condition typically persists for decades.


Scientists at Stanford University School of Medicine (Stanford, CA, USA) analyzed blood samples from 192 patients with ME/CFS, as well as from 392 healthy control subjects. The average age of patients and controls was about 50. Patients' average duration of symptoms was somewhat more than 10 years. Antivirals, anti-inflammatories and immune-modulating drugs had led to symptomatic improvement in some cases, but no single pathogenic agent that can be fingered as the ultimate ME/CFS trigger has yet been isolated.

To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of the ME/CFS patients and the healthy controls were measured using a 51-multiplex array on Luminex 200 IS system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding.

The investigators reported that when comparing patients versus control subjects, they found that only two of the 51 cytokines they measured were different. Tumor growth factor beta (TGF-β) was higher and resistin was lower in ME/CFS patients. However, they found that the concentrations of 17 of the cytokines tracked disease severity, and 13 of those 17 cytokines are pro-inflammatory. One of the cytokines whose levels corresponded to disease severity, leptin, is secreted by fat tissue. Best known as a satiety reporter that tells the brain when somebody's stomach is full, leptin is also an active pro-inflammatory substance. Generally, leptin is more abundant in women's blood than in men's, which could throw light on why more women than men have ME/CFS.

Jose G. Montoya, MD, professor of infectious diseases, and lead author of the study, said, “Chronic fatigue syndrome can turn a life of productive activity into one of dependency and desolation. For decades, the 'case versus healthy controls' study design has served well to advance our understanding of many diseases. However, it's possible that for certain pathologies in humans, analysis by disease severity or duration would be likely to provide further insight.” The study was published on July 31, 2017, in the journal Proceedings of the National Academy of Sciences.