Shephard, Roy J · Critical reviews in immunology · 2002
When people exercise, their muscles release a protein called IL-6 that helps control inflammation and manage energy. This review examines how the body produces different types of inflammatory signals during and after exercise, with IL-6 playing a central role. The authors note that people with ME/CFS have higher levels of these inflammatory proteins, though it's unclear whether these proteins actually cause the fatigue experienced by patients.
This review is relevant to ME/CFS research because it documents that cytokine levels are elevated in ME/CFS patients and discusses potential relationships between exercise-induced immune responses and chronic fatigue. Understanding how normal exercise physiology differs from ME/CFS immune activation is crucial for explaining post-exertional malaise and informing safe exercise recommendations.
This review does not establish that exercise-induced cytokine release causes fatigue in ME/CFS patients—the authors explicitly state this causal link remains unclear. The study does not compare ME/CFS patients directly with healthy controls during exercise, so it cannot demonstrate whether ME/CFS cytokine responses are abnormal in character, magnitude, or duration. This is a literature review, not a primary research study, so it reflects the state of evidence as of 2002 and does not generate new experimental data.
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
Shephard, Roy J (2002). Cytokine responses to physical activity, with particular reference to IL-6: sources, actions, and clinical implications.. Critical reviews in immunology. https://pubmed.ncbi.nlm.nih.gov/12498381/
BibTeX
@article{mecfsatlas-shephard-2002-cytokine-responses,
author = {Shephard, Roy J},
title = {Cytokine responses to physical activity, with particular reference to IL-6: sources, actions, and clinical implications.},
journal = {Critical reviews in immunology},
year = {2002},
note = {PubMed: 12498381},
url = {https://www.mecfsatlas.com/evidence/shephard-2002-cytokine-responses},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/shephard-2002-cytokine-responses
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