Blundell · Brain, behavior, and immunity 2015 · systematic review of case-control studies · n=38 studies

Chronic fatigue syndrome and circulating cytokines: A systematic review.

Cited 172 times in the scientific literature.

Level 3 - non-randomized controlled study

Systematic review of observational case-control studies

PubMed 26148446 · doi:10.1016/j.bbi.2015.07.004 · record verified 2026-08-26

What was done

A PRISMA-compliant systematic review was conducted across PubMed, Web of Science, Embase, and PsycINFO searching for studies comparing circulating cytokines between individuals meeting established chronic fatigue syndrome (CFS) criteria and healthy controls. Included papers were assessed for quality, and data were synthesized on 77 resting serum or plasma cytokines as well as cytokine changes following physical exercise.

What was found

Across 38 included studies, transforming growth factor-beta (TGF-β) was significantly elevated in CFS cases in 5 of 8 studies (63%). No other cytokine was consistently altered across a majority of studies, though data were insufficient for some cytokines. Following physical exercise, circulating cytokine levels did not differ between CFS cases and healthy controls, and exercise did not alter elevated baseline TGF-β levels.

Why it matters

This review shows that standard circulating cytokines do not explain post-exertional fatigue in CFS, although elevated TGF-β warrants further focused study.

Limits

The abstract reports variable quality across the 38 included studies and does not provide total participant counts, exact concentrations, or effect sizes. Many of the 77 measured cytokines had insufficient data across studies to permit reliable conclusions.

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