Heesen, C, Nawrath, L, Reich, C et al. · Journal of neurology, neurosurgery, and psychiatry · 2006 · DOI
This study looked at whether immune system chemicals called cytokines might cause fatigue in multiple sclerosis patients, similar to how infection makes you feel tired and sick. Researchers compared blood samples from 15 MS patients with severe fatigue to 15 MS patients without fatigue, and found that those with fatigue had significantly higher levels of inflammatory molecules. This suggests that immune system activation may be a key driver of MS-related fatigue.
This study provides mechanistic insight into how inflammatory cytokines may drive fatigue in MS, a mechanism potentially shared with ME/CFS given similarities in sickness behavior. Understanding the immune basis of fatigue in MS could inform investigation of similar pathways in ME/CFS and support development of targeted therapies. For ME/CFS patients and researchers, this work strengthens the biological plausibility that immune activation—not psychological factors—underpins post-viral fatigue conditions.
This study does not prove that cytokines are the sole cause of fatigue, only that they correlate with it—other factors likely contribute. It does not establish whether elevated cytokines are the direct cause or a consequence of fatigue, nor does it demonstrate that reducing cytokines would resolve fatigue. The findings in MS patients may not directly transfer to ME/CFS without validation in that population.
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
Heesen, C, Nawrath, L, Reich, C, Bauer, N, Schulz, K-H, & Gold, S M (2006). Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp.2005.065805
BibTeX
@article{mecfsatlas-heesen-2006-fatigue-multiple,
author = {Heesen, C and Nawrath, L and Reich, C and Bauer, N and Schulz, K-H and Gold, S M},
title = {Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2006},
doi = {10.1136/jnnp.2005.065805},
note = {PubMed: 16361589},
url = {https://www.mecfsatlas.com/evidence/heesen-2006-fatigue-multiple},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/heesen-2006-fatigue-multiple
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