Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

This study looked at inflammatory markers in people with persistent fatigue that began after treating Hepatitis C with interferon alpha therapy, and persisted for at least 6 months after. The initial grant described the persistent fatigue and flu-like symptoms occurring after treatment of Hepatitis C with Interferon alpha therapy as being remarkably similar to Chronic Fatigue Syndrome. This study is due to be published in 2019, a corrected proof was made available online in December 2018, and a press release, science briefing and interviews with the media were held in December 2018, ahead of publication.

Funding

 * Medical Research Council grant name: Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome (MR/J002739/1), awarded to Carmine Pariante, the 20th author.


 * "Additional support" from the National Institute for Health Research Mental Health Biomedical Research Centre in Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London, both of which also part supported Trudie Chalder.


 * Principle investigator Alice Russell also received support from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust.

Conflicts of interest

 * This study included a long list of conflicts of interest, almost entirely related to prior hepatitis funding, drug companies that produce treatments for hepatitis and prior funding for research apparently unrelated to ME/CFS.


 * Carmine Pariante, who the Medical Research Council grant was awarded to, also disclosed prior funding on depression and inflammation in the conflicts of interest.

Criticism from scientists

 * Dec 17, 2018, Have scientists found explanation for the onset of ME/CFS? - Nick Brown
 * Dec 18, 2018, Trial By Error: The New Interferon “CFS” Study - David Tuller

Responses and criticism from charities

 * Charity Action for ME welcomed the study, but criticized the choice of diagnostic criteria, stating it did not include post-exertional malaise, the "hallmark" symptom of ME/CFS, which could lead to patients with other non-fatiguing conditions being included
 * #MEAction Missing Millions urged caution

Criticism from citizen scientists

 * "This lower KYN/TRP ratio in #CFS is somewhat in opposition to a study of somatization which observed higher levels of the KYN/TRP ratio. This points to a different biological underpinning of primarily psychiatric syndromes, such as depression & somatization, as opposed to CFS."  - Tom Kindlon
 * Science4ME forum

Investigators
Alice Russell, Nilay Hepgul, Naghmeh Nikkheslat, Alessandra Borsini, Zuzanna Zajkowska, Natalie Moll, Daniel Forton, Kosh Agarwal, Trudie Chalder, Valeria Mondelli, Matthew Hotopf, Anthony Cleare, Gabrielle Murphy, Graham Foster, Terry Wong, Gregor A. Schütze, Markus J. Schwarz, Neil Harrison, Patricia A. Zunszain, Carmine A. Pariante

Media coverage
This study has had media coverage, and a briefing for journalists was held at the Science Media Centre, UK.
 * 2018, Could overactive immune system trigger Chronic Fatigue Syndrome?
 * 2018, First look at sufferers before they fall ill suggests overactive immune system can put them 'on trajectory' to years of exhaustion
 * 2018, Study finds chronic fatigue clues in overactive immune response
 * 2018, Chronic fatigue syndrome 'could be triggered by overactive immune system'

Learn more

 * CFS/ME Ongoing Projects - grant MR/J002739/1 - Medical Research Council