Russell, Alice, Hepgul, Nilay, Nikkheslat, Naghmeh et al. · Psychoneuroendocrinology · 2019 · DOI
This study suggests that some people treated with interferon-alpha (a drug used for hepatitis C) develop persistent fatigue that continues even after treatment ends—similar to ME/CFS. Researchers found that people who later developed long-lasting fatigue had a stronger immune response early in treatment, with higher levels of certain immune molecules. Importantly, the fatigue persisted even after the immune trigger was gone, suggesting that something in the body's initial overreaction may set off a lasting problem.
This study offers a novel opportunity to observe immune activation *before* and *during* a trigger in controlled conditions, overcoming a major limitation in ME/CFS research—the inability to measure baseline immune status. By identifying an exaggerated early cytokine response in those who develop persistent fatigue despite immune trigger resolution, the study suggests a mechanistic link between initial immune dysregulation and chronicity, potentially pointing to preventable pathways.
This study does not prove that interferon-alpha-induced fatigue is identical to ME/CFS or that the same mechanisms cause both; it is a model system with inherent limitations in mimicking natural viral or infective triggers. It does not establish causation between cytokine elevation and persistent fatigue—only correlation—and cannot explain why some individuals experience persistent fatigue while others do not, despite similar immune activation. The absence of peripheral inflammation post-treatment does not exclude central nervous system immune involvement or other unmeasured biological processes.
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
Russell, Alice, Hepgul, Nilay, Nikkheslat, Naghmeh, Borsini, Alessandra, Zajkowska, Zuzanna, Moll, Natalie, et al. (2019). Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome.. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2018.11.032
BibTeX
@article{mecfsatlas-russell-2019-persistent-fatigue,
author = {Russell, Alice and Hepgul, Nilay and Nikkheslat, Naghmeh and Borsini, Alessandra and Zajkowska, Zuzanna and Moll, Natalie and Forton, Daniel and Agarwal, Kosh and Chalder, Trudie and Mondelli, Valeria and Hotopf, Matthew and Cleare, Anthony and Murphy, Gabrielle and Foster, Graham and Wong, Terry and Schütze, Gregor A and Schwarz, Markus J and Harrison, Neil and Zunszain, Patricia A and Pariante, Carmine M},
title = {Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome.},
journal = {Psychoneuroendocrinology},
year = {2019},
doi = {10.1016/j.psyneuen.2018.11.032},
note = {PubMed: 30567628},
url = {https://www.mecfsatlas.com/evidence/russell-2019-persistent-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/russell-2019-persistent-fatigue
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