Review Chronic fatigue syndrome and circulating cytokines: A systematic review, 2015, Blundell, White et al.

[SNT Gatchaman]

Chronic fatigue syndrome and circulating cytokines: A systematic review
S Blundell, KK Ray, M Buckland, PD White

There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS.

Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS relatedterms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality.

38 papers met the inclusionary criteria. The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of Transforming Growth Factor-beta (TGF-β) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines. Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-β concentrations.

The finding of elevated TGF-β concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue.

Link | PDF (Brain, Behavior, and Immunity)

 

[SNT Gatchaman]

This paper from 2015 predated S4ME's founding but is probably worth having listed.

 

[Creekside]

That's good to have for whenever someone claims that it must be circulating cytokines. We should have an official list of theories that have been reasonably disproven.

 

[bobbler]

Interesting that PD White is one of the authors

 

[SNT Gatchaman]

Yes, I posted it because it was referenced in a recent preprint —

In this cohort, there were notable perturbations in innate and early adaptive immunity during acute infection that correlated with development of LC. Proliferating NK cells in males showed bidirectional TGF-β signaling, which would be expected to reduce NK cell cytotoxicity, as previously observed in severe COVID-19 (161), which may limit the efficacy of the initial antiviral response. Increased TGFβ1 expression was also found to be associated with LC development and persistence across many cell types, including naive and memory T cells, which may lead to reduced T helper 1 (Th1) differentiation (162) and impaired immunity against intracellular pathogens. Conversely, TGF-β signaling contributes to regulatory T cell differentiation, which may be important for avoiding self-reactivity (163). Interestingly, TGF-β has been previously suggested to play a role in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (164) and was described to be increased in the plasma of males with LC in a pre-print study of a different LC patient cohort (165).

164 is this paper.

 

[Jonathan Edwards]

This paper from 2015 predated S4ME's founding but is probably worth having listed.

It is an important milestone that was well aired in the pre-S4ME days. I think it was presented in Bristol in 2014. TGF beta should probably be taken seriously. The conclusion is fair but only in the sense that serum levels are clearly not the whole story. That would not be at all surprising since many, if not most, cytokines are designed to operate at close range, not in circulation.