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New CFS and inflammation paper

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13,774
http://www.sciencedirect.com/science/article/pii/S0165032712002352

Review
Inflammatory fatigue and sickness behaviour — Lessons for the diagnosis and management of chronic fatigue syndrome

  • S.V. Arnett , ,
  • I.A. Clark
  • Research School of Biology, Australian National University, Australia

Abstract

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management.



(I've got no comment, and tend not to read papers like this, but thought it might be of interest to others... and then you can let me know what you think too!)
 

heapsreal

iherb 10% discount code OPA989,
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10,086
Location
australia (brisbane)
I think one of the theories of when we have a crash, is that it is a cytokine storm etc which causes an increase in symptoms. If there was some type of anti-inflammatory effective againts cytokines, then we may be able to avoid crashes, maybe???
 

Don Quichotte

Don Quichotte
Messages
97
I read it briefly, but it seems to be an excellent and well-balanced review article. ( I am not a CFS expert, so maybe there is nothing new for you there).

Reading it I was just thinking (and this may be totally far-fetched).

Myelofibrosis is a fatal disease in which there is gradual scarring of the bone marrow.

mutations in JAK-2 were found to play a significant role in this disease, and therefore a JAK-2 inhibitor was developed.

Surprisingly, it did very little to alter the course of the disease, but it had a significant effect on constitutional symptoms (fatigue, anorexia etc).
This agent led to significant inhibition of inflammatory cytokines.

you can read about it here- http://www.sciencedaily.com/releases/2010/09/100915171526.htm

JAK-2 inhibition may also play a role in T cell regulation.

http://www.ncbi.nlm.nih.gov/pubmed/21917753

If indeed CFS is a disease in which an abnormal inflammatory response plays a significant role, maybe it could be a possible treatment option.
 

ramakentesh

Senior Member
Messages
534
Of interest - when i overdo things I find that I either get a relapse of CFS/POTS or a relapse of Ankylosing Spondylitis, a condition characterised by increased activation of pro inflammatory cytokines
 
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43
Folks, Ive just read through this paper. Its probably one of the best overview papers Ive read in the last 3-4 years and as an ME/CFS sufferer, who has spent the last few years reading and reading and formulating ideas in my mind (with my main idea being that an intra-cellular pathogen tiggers an immune response that fails, thus a secondary immune response is needed, Th1 to Th2 but other finer details like increased cellular Mast cell activity which results in chemical sensitives, and the hyper-immune state calls into action a host of immune respones like cytokines, TNF-a, IL's and so on, which at the cellular level disrupt normal processes, leading to increases NO and free radicals and waste products from the immune cells themselves, which all lead to a shift in body energy productiona and storage, that leads to cellular level stress and body fatigue - along with loads of changes in neurophysiology and brain activities, ie the brain responding to the insult and abnormal status of brain inflammation by inducing extra fatigue and protective behaviours)..overall this paper reveals I am and have been right on track with whats happening in my body and I know exactly that this is true because I feel it every day.

Its just a shame its taken 55 years since Ramsay said very similar things in London at the Royal Free Hospital about his patients, until today 2012, and this is in no part a result of the interference of very biased and self-serving pyschiatrists who manipulated medical science, disorted research, shifted focus away from cells to mental health issues, created unproveable psychological models of somatistaion, jumped into bed with insurance companies and Governments who's only motives have been to save money; all the while research was halted and patients suffered at the hands of general doctors who denied them, rejected them, or subjected them to brain washing, while Governments denied benefits.

Papers like this are changing the landscape and its thanks in part to Maes and Twisk and handful of Belgium researchers who have gone against orthodoxy and rejected psychobabble in favour of listening to the patients they saw.

This paper says something that sums up my view: "The neurophysiology of sickness behaviour has been attributed to direct actions of inflammatory cytokines on neurons ( [Butler et al., 2004], [Cumiskey et al., 2007], [Janelsins et al., 2008] and [Sheng et al., 1996]), "

thats what ME is my friend, an immune disease involving neurons that probably also affects muscles or at least most cells in your body, that causes you to feel sick and tired.

Just wanted to add the one down side of this paper is it makes no real attempt to clarify the potential causes ie the viral or bacterial triggers and the focus is on down stream management rather than on the removal of the trigger or underlying cause ie any virus or bacteria.
 

Guido den Broeder

Senior Member
Messages
278
Location
Rotterdam, The Netherlands
According to unpublished results from a study in The Netherlands (Prof. Drexhage, Erasmus MC, Rotterdam), the cytokine response is indeed off in post-EBV ME. The profile established so far is different from that in some other diseases, but not entirely unique.

There is a current attempt to develop a simple test.

Btw, Twisk is also Dutch. He is a patient.
 
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13,774
Thanks for the comments. I don't normally read papers like this, but thought it seemed potentially interesting.
 

Desdinova

Senior Member
Messages
276
Location
USA
Eh not bad, but I can't stand the use of this term "sickness behaviour". Yeah like I can just apply myself and use a little self control and it goes away.:rolleyes:
 

Xandoff

Michael
Messages
302
Location
Northern Vermont
New CFS and inflammation paper

This explains a lot....I think. It explains my inflammation and pain storms! Thanks for posting Esther12!
 

ramakentesh

Senior Member
Messages
534
thats what ME is my friend, an immune disease involving neurons that probably also affects muscles or at least most cells in your body, that causes you to feel sick and tired.

- I also like this hypothesis. Consider it from the autoimmune v infectious ilness paradigm. How many infecteous illnesses have an 80% female ratio? How many wax and wane in many?

Not many if any, but many autoimmune illnesses most certainly do.
 

Dolphin

Senior Member
Messages
17,567
I thought this was interesting:
Production of reactive oxygen and nitrogen species is an important effector arm of the immune system as these compounds are highly toxic to a broad range of microorganisms (Roos, 1991) and can function as second messengers in signal transduction pathways (Forman and Torres, 2001)
So, in theory, if one had a chronic infection one might even want high levels/reducing them (in the non-chemical sense) might not even be desirable.
 

Adster

Senior Member
Messages
600
Location
Australia
Interesting paper, but the term sickness behavior is probably not going to be kind to us if it gains traction.
 
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646

urbantravels

disjecta membra
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1,333
Location
Los Angeles, CA
"Sickness behavior" is one of those terms of art that is just horribly, hideously misleading to any general reader.

It's a phrase that has some usefulness to a particular line of biomedical research, but once it escapes the very limited circles in which certain scientists know what it means, it is almost completely inevitable that it gets folded into the narrative about chronically ill people just "acting" sick through conscious, volitional choices - and that a choice of different behaviors would magically make the person "less ill". You know the drill. Wessleyite faith healing - you'll feel better if you stop thinking of yourself as sick!

"Sickness behavior" is kind of a mixed bag of stuff, and it's hard to draw a bright line between "voluntary" and "involuntary" "behaviors." Is "sickness behavior" simply the result of being weak and tired - say, diminished aerobic capacity due to some disease process - or is it the result of brain chemical signaling which *indirectly* motivates you to lie down and rest, in order to reserve more energy for fighting infection - or is it various mixtures of both, and other factors?

Obviously, natural selection would tend to give us traits that increase our likelihood of surviving an illness, but "total immobilization" isn't a great strategy either, so there's some kind of compromise at work in most illnesses. In any given illness situation, you usually have *some* reserves you can draw upon for an emergency. Since we generally have more complex decisions to make than "Should I attempt to escape from this burning building?", we constantly have to weigh the pros and cons of dragging ourselves through X activity, both in terms of energy budget and in terms of "How badly will I get beaten up for this later by the PEM/PENE thugs?"

Since we need to have consciousness and memory to associate overexertion with delayed PEM/PENE, I have trouble seeing PEM/PENE as primarily an evolutionary adaptation gone wrong. I don't think "sickness behavior" by itself can explain all the pathology of ME/CFS, although it may be playing a role.
 

Xandoff

Michael
Messages
302
Location
Northern Vermont

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
Simon Arnett provided an outline of key concepts in the full text article at:
http://www.prohealth.com/library/showarticle.cfm?LIBID=16982

Am finally reading through the paper now Mr D, sir [salutes] :)

Thanks for that and for this:

“This review is an attempt to provide an overview of what is known about the changes that occur in CFS, and how these changes might be explained by an inflammatory process. This explanation draws on what is known about a process called 'cytokine-mediated sickness behavior'.

Sickness behavior is a very well studied cluster of neurological and behavioral changes that occur when the brain is exposed to increased inflammatory mediators, and is similar in many regards to CFS.

“It is therefore argued that CFS may be a syndrome in which the normal processes of sickness behavior malfunction to produce the debilitating lived experience of CFS.

“This review also discusses the search for a blood test for CFS. This discussion focuses on a test for increased oxidation, which has been proposed by several other authors. However, using this blood test could be dangerous, as it cannot distinguish chronic fatigue syndrome from other conditions such as cancer and autoimmune disease, which can cause symptoms very similar to CFS.

“Finally, the review argues that if CFS is the result of a similar process that produces cytokine mediated sickness behavior, then targeting this process with anti-cytokine therapy (using drugs such as etanercept and anakinra) should be effective in improving patient symptoms."

I'm assuming Prohealth asked and this was the author's reply. This is cool. I probably have read it explained like this before - but forgot or haven't bothered looking. It gets raised of course as a 'negative' term hung around our necks but if this is a more reasonable explanation then it might be of significant help for others who are put out by the term.

I suspect different scientists and academics have phrased their definitions differently, and perhaps more importantly how they consider these responses are treated (Ha!) and I'll now check out old IVI's definition too :)

Edit:

Yes. It is as I expected:

It is also important to recognize that other animals may recognize sickness behavior as a sign of weakness and mark the victim out for targeting by predators.

http://journals.cambridge.org/actio...C7169097.journals?fromPage=online&aid=1889668

Now you know!! :)