Blundell, S, Ray, K K, Buckland, M et al. · Brain, behavior, and immunity · 2015 · DOI
Researchers reviewed 38 studies looking at whether immune proteins called cytokines are elevated in people with ME/CFS. They found that one specific cytokine, TGF-β, was consistently higher in people with ME/CFS compared to healthy people in about 63% of studies. However, most other immune proteins measured were normal, and exercise did not change cytokine levels differently between people with ME/CFS and healthy controls.
Understanding whether immune dysregulation drives ME/CFS is crucial for developing targeted treatments. This review clarifies that circulating cytokines alone do not explain the hallmark post-exertional malaise symptom, but identifies TGF-β as a candidate for further investigation, potentially redirecting research toward more specific immune mechanisms.
This review does not prove that cytokines play no role in ME/CFS—it shows that abnormal circulating levels are not the primary explanation. Elevated TGF-β correlation does not establish causation. The study also cannot determine whether other immune markers (intracellular cytokines, tissue-level inflammation, or immune cell subsets) might be abnormal, as it focused only on serum and plasma measurements.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Blundell, S, Ray, K K, Buckland, M, & White, P D (2015). Chronic fatigue syndrome and circulating cytokines: A systematic review.. Brain, behavior, and immunity. https://doi.org/10.1016/j.bbi.2015.07.004
BibTeX
@article{mecfsatlas-blundell-2015-chronic-fatigue,
author = {Blundell, S and Ray, K K and Buckland, M and White, P D},
title = {Chronic fatigue syndrome and circulating cytokines: A systematic review.},
journal = {Brain, behavior, and immunity},
year = {2015},
doi = {10.1016/j.bbi.2015.07.004},
note = {PubMed: 26148446},
url = {https://www.mecfsatlas.com/evidence/blundell-2015-chronic-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/blundell-2015-chronic-fatigue
Contribute
Private, reviewed by a human. Not a public comment thread.