Tsilioni, Irene, Natelson, Benjamin, Theoharides, Theoharis C · The European journal of neuroscience · 2022 · DOI
This study found that after exercise, patients with ME/CFS have more pieces of DNA from their mitochondria (the energy-producing parts of cells) floating in their blood inside tiny particles called exosomes. When researchers tested these exosomes on immune cells in the lab, they triggered the release of IL-1β, a chemical that causes inflammation in the brain. This suggests that exercise might trigger a chain reaction involving these DNA-carrying particles that could contribute to ME/CFS symptoms.
This study identifies a potential biological mechanism that could explain why ME/CFS patients experience symptom flares after physical activity—a hallmark feature called post-exertional malaise. Understanding this mechanism is crucial for developing targeted treatments that address the underlying cause rather than just managing symptoms. The findings also suggest that exosomal mtDNA and microglial activation could serve as measurable biomarkers to help diagnose and monitor ME/CFS.
This study does not prove that exosomal mtDNA and IL-1β elevation directly cause ME/CFS symptoms in patients, only that this mechanism occurs in laboratory conditions. It also does not establish whether blocking IL-1β would improve ME/CFS symptoms or whether mtDNA elevation is the primary cause versus a consequence of other disease processes. Additionally, the study does not confirm that post-exertional mtDNA elevation occurs consistently across all ME/CFS patients or determine optimal exercise thresholds that trigger this response.
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
Tsilioni, Irene, Natelson, Benjamin, & Theoharides, Theoharis C (2022). Exosome-associated mitochondrial DNA from patients with myalgic encephalomyelitis/chronic fatigue syndrome stimulates human microglia to release IL-1β.. The European journal of neuroscience. https://doi.org/10.1111/ejn.15828
BibTeX
@article{mecfsatlas-tsilioni-2022-exosome-associated,
author = {Tsilioni, Irene and Natelson, Benjamin and Theoharides, Theoharis C},
title = {Exosome-associated mitochondrial DNA from patients with myalgic encephalomyelitis/chronic fatigue syndrome stimulates human microglia to release IL-1β.},
journal = {The European journal of neuroscience},
year = {2022},
doi = {10.1111/ejn.15828},
note = {PubMed: 36153118},
url = {https://www.mecfsatlas.com/evidence/tsilioni-2022-exosome-associated},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/tsilioni-2022-exosome-associated
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