Chronic fatigue syndrome and circulating cytokines: a systematic review

Chronic fatigue syndrome and circulating cytokines: a systematic review

• S. Blundella,
• K.K. Rayb,
• M. Bucklandc,
• P.D. Whitea,

Abstract:

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Highlights
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Circulating TGF was raised in CFS versus controls in most studies when measured.

•
No overall differences were found for any other cytokines.

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There were no overall differences in cytokine concentrations after exercise.

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The quality of studies published was variable and often limited.

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.

Keywords

• Chronic fatigue syndrome;
• Myalgic encephalomyelitis;
• Cytokine;
• Chemokine;
• Transforming growth factor-beta;
• Immune system;
• Pathophysiology;
• Systematic review

Corresponding author.
Copyright © 2015 Published by Elsevier Inc.

 

Exercise in futility. Did they not read the Lipkin paper? Early and late stage ME cytokine findings cancel each other out if you just combine groups without regard for duration of illness.

 

What do you expect?

P.D. White

 

I expect incompetence but I'm ranting for the benefit of others who may be reading PR.

 

I've heard about P.D. White before. Is he part of the psychosomatic camp?

Also, it seems ridiculous that they put this review together and lumped early sufferers and later patients together like that. It's not sensible, given the data available....

-J

 

Notorious psychobabbler from the UK. Two words: PACE trial.

 

Oh dear. Got it.

 

I was going to type this, word for word the same! Great minds ...

 

I really don't like that this seems to have been written in a direct attempt to refute Hornig's study. Doctors without a lot of time will scan this and think, "ah, I knew that was all bunk". I wish there were some magic that would make people less intellectually lazy!

In the past, I would have said 'education' was that magic, but it's really the quality of the education, not its quantity, that matters. I'm sure these guys consider themselves very learned men.

 

It feels cheap and cynical, as much of his stuff does. But it's interesting to compare his reaction to the changing situation (denial, obfuscation, sabotage) with Wessely's (equivocation, positioning).

Of course Wessely is the consummate politician and, perhaps most importantly, has his main career outside CFS research these days - he just needs to keep on the right side of things now and, such was his ambiguous postion, no-one will much notice if he was wrong before. You can be sure no-one will pay any attention to our howls of protest.

Whereas White is absolutely embedded in CFS still - it's where he makes his money, both as a researcher and a "consultant". I suspect he won't go down without a fight and watching the death of his career in the aftermath won't be pretty.

Popcorn anyone? (accounting for allergies, obviously)

 

I'm wading through the paper.

 

They know they can't produce robust evidence for their theories or therapies. The only thing that's left is producing a lot of bullshit while trying to maintain the appearance of good work. Sheer quantity and doubt. That doesn't work forever - eventually the biological basis of the illness is understood and they have to find some new poorly understood illness to parasitize.

 

Yes. They also would use the broadest CFS definition possible, so ME, CFS, and fatigue trials would all get reviewed as if they are discussing the same disease. It's meaningless, like most of their work.

 

He's also part of the Disability Insurers Profit Protection Team.

 

Sir Simon the Weasel sure is impressed with himself.

 

IMO, this "study" looks less like an effort to find something, and more like a deliberate attempt to find nothing so that they can continue to claim there are no physical abnormalities in ME/CFS. They are very good at manipulating their data -- in this case by selecting the studies they use and ignoring new and significant studies -- so they get the results they want. This is not scientific research designed to uncover new information; it's propaganda designed to obscure what they consider to be unacceptable information. It's appalling that this gets published as science. I blame incestuous reviewing practices which avoid the "problem" of unbiased reviewers asking uncomfortable questions.

 

Hornig / Lipkin cytokine study released 27 February 2015

 

White may have inadvertently done us a favour in highlighting TGF-β and it's inhibitory effect on activated leucocytes (which include microglia).

It appears that TGF-β plays a key role in battling neuroinflammation but it's inhibitory capacities can be undermined :

LPS antagonism of TGF-β signaling results in prolonged survival and activation of rat primary microglia

http://onlinelibrary.wiley.com/doi/10.1111/jnc.12612/abstract

You would expect that microglial survival would be a good thing - not when they're inappropriately activated and neurotoxic. Is the paradoxical association of the upregulation of normally protective TGF-β with a range of 'neuroinflammmatory' disorders a compensatory reaction to blocked signalling?

 

They did include the Hornig 2015 study but if I understand their table correctly they just extracted data for the whole group of 298 participants which, as we know, is very misleading since the cytokine pattern in that study changed over time.

 

I would just add that TGF-β is often sky-high in CFS patients who've had it measured by certain "mold doctors" who have taken some heat here recently.