Psychiatrists Review Cytokine Studies in ME/CFS - Find Little

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Not sure why Peter White is interested in cytokines. Mary Fletcher, I believe it was, said that many studies don't use to date techniques but that their lab consistently finds cytokine issues in ME/CFS.

That said it's true there's very little consistency in the literature. Cytokine levels may not matter much of even small increases in cytokines are enough to set off the microglia. Plus Broderick believes that even normal levels of some cytokines can set off a bizarre reaction if the immune network itself is tweaked. Younger on the other hand, used networking analysis I think it was to identify leptin as the key driver of symptoms in the good day/bad day study...I believe it was only mildly elevated otherwise.

It's a very complex subject with new ways emerging how to analyse it.
Exercise has been associated with C4a (complement) increases in the blood or in gene expression in two studies. That apparently didn't make the paper.

TBG-B, however - the one cytokine that was consistently abnormal - could be important. The paper said"

The observations therefore seem to be consistent with a biologically significant elevation in the cytokine concentration in CFS. The clinical significance of a raised TGF-β is unclear in CFS, but its associations with clinical symptoms, severity and prognosis merits further evaluation.

As an immune mediator, TGF-β has both pro- and anti-inflammatory effects. The intracellular signal transduction, following engagement of the TGF-β receptor, depends upon the cell type and context in which the cell is activated.

TGF-β's inhibitory effect on activated leukocytes means it could be turning the immune system down. It may be attempting to turn off activated microglia; that is increased TGF-B may be a sign of neuroinflammation. TGF-β is also associated with alterations in cerebral blood flow (Gaertner et al., 2005). It also appears to depress motor activity and it's associated with increased free radical production during exercise. It's an interesting cytokine...


Brain Behav Immun. 2015 Jul 3. pii: S0889-1591(15)00238-X. doi: 10.1016/j.bbi.2015.07.004. [Epub ahead of print] Chronic fatigue syndrome and circulating cytokines: a systematic review. Blundell S1, Ray KK2, Buckland M3, White PD4.
Author information

  • 1Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom.
  • 2East London Foundation NHS Trust, London, UK.
  • 3Barts Health Trust, London, UK.
  • 4Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom. Electronic address: p.d.white@qmul.ac.uk.
Abstract

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 related-terms 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-) 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.
 

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