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The role of IP-10 in Chronic Fatigue Syndrome

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
From here: http://www.fasebj.org/content/31/1_...utm_medium=cpc&utm_campaign=FASEB_J_TrendMD_0

The role of IP-10 in Chronic Fatigue Syndrome.
  1. Anne McArdle1,
  2. Arief Gusnanto2,
  3. Kate Earl1,
  4. George Sakellariou1,
  5. Clare Lawton2,
  6. Daniel Owens3,
  7. Graeme Close3,
  8. Michael Beadsworth1 and
  9. Louise Dye2
+Author Affiliations

  1. 1University of Liverpool, Liverpool, United Kingdom
  2. 2University of Leeds, Leeds, United Kingdom
  3. 3Liverpool John Moores University, Liverpool, United Kingdom
Abstract
Chronic fatigue syndrome (CFS) is a severely debilitating and complex illness of uncertain cause, characterised by prolonged, fatigue triggered by minimal activity.

There is evidence that CFS is associated with chronic inflammation. Studies have shown that plasma levels of cytokines are chronically modified in patients with CFS. This study examined physiological, subjective and cognitive factors associated with plasma cytokine concentrations in a cohort of 92 patients compared with age and sex matched healthy controls.

A sub-group of patients and healthy controls (HCs) also underwent more detailed analyses of muscle function, cytokine production and cognitive function.

Patients were diagnosed with CFS if they met the Oxford criteria for Chronic Fatigue Syndrome and recommended NICE guidelines. Patients completed a number of validated questionnaires including the Chalder Fatigue Questionnaire (CFQ) which is considered a valid and reliable measure of fatigue in patients with CFS.

Patients with CFS demonstrated a characteristic significant reduction in Maximal Voluntary Contraction Force compared with HCs.

Data on plasma concentrations of 27 pro- and anti-inflammatory cytokines were analysed using multiple or logistic regression with age and sex which were significant covariates included in each model.

CFS was strongly associated with a limited number of cytokines. Diagnosis of CFS was associated with increased plasma contents of MIP-1a, MIP-1b and RANTES (p<0.05) and marginally with Eotaxin (p=0.07) when modelled individually. MVC and self-reported fatigue both showed particularly strong associations with plasma IP-10 concentrations.

Muscle content of IP-10 mRNA was significantly elevated, suggesting that, at least in part, muscle was a source of this IP-10 but not the other cytokines.

Pairwise associations between MVC and cytokines demonstrated that the reduced MVC seen in patients with CFS was strongly associated with plasma levels of IP-10, TNF-α and IL-5. Further analyses revealed strong correlations between plasma RANTES and eotaxin levels and poorer verbal recall and RTs of patients with CFS.

The consistent association of IP-10 with the physiological features and of RANTES and eotaxin with the cognitive features of CFS provides compelling evidence for a role of these cytokine/chemokines in the physiological and cognitive pathology of CFS.

This work was funded by the Medical Research Council.

Support or Funding Information

This work was funded by the Medical Research Council.
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Beginning to think that eotaxin is a pretty common finding now. This is not the first or second study I've seen this. Also, some of what they're saying is elevated provokes the production of interferon -- also found elevated multiple times in ME/CFS.

QMUL would never have produced such a paper, but it's good to see that other universities in the UK are on the ball.
 

*GG*

senior member
Messages
6,389
Location
Concord, NH
Beginning to think that eotaxin is a pretty common finding now. This is not the first or second study I've seen this. Also, some of what they're saying is elevated provokes the production of interferon -- also found elevated multiple times in ME/CFS.

QMUL would never have produced such a paper, but it's good to see that other universities in the UK are on the ball.

Can you break up the Post to make it easier to read? I wonder what the Conclusion is/were?

GG
 

Mohawk1995

Senior Member
Messages
287
Two things that amaze me about these discussions:
  1. That these systemic biochemical and biomolecular pathologies can be so widespread across so many different fronts in the body.
  2. That our bodies when functioning properly are able to manage all of these different substances and keep them in balance so we are able to function properly.
Both speak to the immeasurable complexity of the human body!
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
thanks, Not expert on the different diagnositc criteria, but isn't Oxford rather weak criteria? Catches a lot of psychological diseases as well, correct?

GG
According to the abstract, and I have not read the full paper, they also used the NICE guidelines, which are much stronger than Oxford. Why didn't they just drop Oxford entirely?
 

John Mac

Senior Member
Messages
321
Location
Liverpool UK
thanks, Not expert on the different diagnositc criteria, but isn't Oxford rather weak criteria? Catches a lot of psychological diseases as well, correct?

GG

Patients for this study were supplied by the Liverpool CFS clinic which was being run by Dr Alistair Miller who left to be Action for ME's medical adviser.
 

aaron_c

Senior Member
Messages
691
According to the abstract, and I have not read the full paper, they also used the NICE guidelines, which are much stronger than Oxford. Why didn't they just drop Oxford entirely?

I saw that Naviaux used ICC, CCC and Fukuda (you had to qualify for all of them) in the metabolomics paper. I assumed it had something to do with showing up when you googlescholared CFS and Fukuda...but they both puzzle me.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
@JaimeS

Not sure if its me but your link doesn't appear to work on my PC

Sorry, works for me. :(

I saw that Naviaux used ICC, CCC and Fukuda (you had to qualify for all of them) in the metabolomics paper. I assumed it had something to do with showing up when you googlescholared CFS and Fukuda...but they both puzzle me.

I think it's smart. If anyone says "but your research can't be compared in the US, where we predominantly use Fukuda" the answer is "patients met Fukuda too". It works well in transitioning to the use of more stringent criteria, and I think it'll be how things are going to be, moving forward. For example, a recent grant I just saw from the NIH required that patients meet two, specific criteria. I think it was Fukuda and Candian, but don't quote me on that.

-J
 

AdamS

Senior Member
Messages
339
  1. 2University of Leeds, Leeds, United Kingdom
Woo, I went to Leeds Uni, might donate myself to them for research purposes :rofl:

Patients were diagnosed with CFS if they met the Oxford criteria for Chronic Fatigue Syndrome and recommended NICE guidelines.

Lol.

Patients with CFS demonstrated a characteristic significant reduction in Maximal Voluntary Contraction Force compared with HCs.

Really? Didn't realise this was characteristic, I can probably still lift roughly the same amount, but if I exceed 4-5 reps i'll collapse!

Muscle content of IP-10 mRNA was significantly elevated, suggesting that, at least in part, muscle was a source of this IP-10 but not the other cytokines.

Cool. Any use in trying to inhibit IP-10 or is that just like putting a bandage over a wound?

Jokes aside, it is nice to see some top UK institutions working on ME/CFS, I know we're way off the pace in this country but we do have some great talent and it would be awesome if we could collab with other great countries such as USA, Norway, Australia, Canada (tell me off if i've missed one) to find a cure!
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
awesome if we could collab with other great countries such as USA, Norway, Australia, Canada (tell me off if i've missed one)
You don't hear much about it in the English language, but I wonder how the very large and well funded program in Japan is going. There are also several other places in Europe doing things, though with limited funding.
 

nandixon

Senior Member
Messages
1,092
CFS was strongly associated with a limited number of cytokines. Diagnosis of CFS was associated with increased plasma contents of MIP-1a, MIP-1b and RANTES (p<0.05) and marginally with Eotaxin (p=0.07) when modelled individually. MVC and self-reported fatigue both showed particularly strong associations with plasma IP-10 concentrations.
@JaimeS, do you happen to know whether Ron Davis has tested Rapamune (sirolimus aka rapamycin) with CFS blood and his impedence measuring device?

In a 2014 study it was found that:

Conclusion
Sirolimus downregulates the expression of chemokines in monocytes, including MCP-1, RANTES, IL-8, MIP-1α, and MIP-1β, by inhibiting the NF-κB-p65 and MAPK-p38 signalling pathways.

(@eljefe19 may be trying rapamycin sometime soon.)