Hornig/Lipkin cytokine study out now - press release

A.B.

A.B.

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If CFS was associated with a lack of serotonin in the brain then SSRIs should work well. I find they just make me more tired. And many CFS patients don't find them useful.

PS: speaking about 5-htp, I can tolerate that and find it helpful for mood but nothing else.
 
MeSci

MeSci

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A.B. said:
If CFS was associated with a lack of serotonin in the brain then SSRIs should work well. I find they just make me more tired. And many CFS patients don't find them useful.

PS: speaking about 5-htp, I can tolerate that and find it helpful for mood but nothing else.
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I tried fluoxetine in early ME, for the serious depression I also had. It just made me more wired and jittery and worsened the difficulty I had sleeping.

I started 5-HTP after a sad event in 2013 that led to an existential crisis, and it has helped significantly with no adverse effects.
 
Kati

Kati

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MeSci said:
I'm not registered with Medscape and don't wish to add to my huge numbers of logins. Can you quote the gist of it, or an extract? Maybe it has also appeared somewhere else.
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Yes I will on my orinigal post.
 
Sushi

Sushi

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msf said:
The author then suggests supplementing with 5-HTP, since this will not be catabolized by IDO.
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My doc has me supplementing 5-HTP due to our "theorized" lack of serotonin. I do well with it.

Sushi
 
M

msf

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Hi Sushi, I think we have the same doctor...he hasn't prescribed 5-HTP in my case, but that might be because I am taking trazadone.
 
M

msf

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AB, I have heard KDM say that SSRIs sometimes don't work in ME patients because there is not enough serotonin for them to act on - this seems to be my experience with Trazadone, sometimes it works well and sometimes it doesn't work at all (this could also be due to down-regulation of the serotonin transporter).
 
nandixon

nandixon

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msf said:
RE: Interferon-gamma interfering with serotonin production, I found this article to be an excellent (although somewhat dense) summary:

http://ceri.com/fftrypto.htm

If the author is right it might not be a good idea simply to supplement tryptophan, since this will also increase quinolinic acid, which is already raised because of overexpression of IDO. The author then suggests supplementing with 5-HTP, since this will not be catabolized by IDO.
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The study that's the topic of this current thread found that interferon-gamma (IFNγ), while higher in short-duration (<3 yrs) patients, actually appeared to be lower in long-duration (>3 yrs) patients relative to the controls.

Lower IFNγ seems consistent, too, with the lower natural killer cell activity often talked about in ME/CFS/SEID, since NK cells are a significant source of IFNγ. (I think at least one large study may be underway or starting soon to verify that lower NK cell activity.)

So, only looking at things with respect to IFNγ, this would seem to mean that in long-duration patients that indoleamine 2,3-dioxygenase (IDO) is more likely under-expressed and that the kynurenine pathway is not functioning as well as it should (IDO being the rate-limiting enzyme for that pathway and being induced by IFNγ).

Thus, in those long-duration patients, more tryptophan should theoretically be available for serotonin synthesis rather than less. That might explain the negative SSRI response in many of us (and might also be consistent with a central fatigue theory, i.e., excess serotonin, playing some part).

Obviously though, there are some long-duration ME/CFS/SEID patients who feel better with SSRI's, so things are clearly not so simple. (Also see this post on a different thread for another, possibly relevant theory regarding there being too little serotonin in ME/CFS.)

So when the authors state:
We hypothesize that IFNγ-mediated lesions in kynurenine metabolism may culminate in the depression and psychomotor retardation that contribute to disability in some patients with ME/CFS (34–36).
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they presumably must be referring to long-term effects of high IFNγ in the short-duration patients. (Otherwise, they seemingly have forgotten their own findings of lower IFNγ in long-duration patients, or are giving no significance to it relative to the controls.)
 
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cigana

cigana

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Gijs said:
For example: il17a is not consistent [1] and Lipkin et al., think it is a very important finding. So his ‘house’ is not build on solid ground.
1. Journal of Translational Medicine 2009, 7:96 Plasma cytokines in women with Chronic Fatigue Syndrome Mary Ann Fletcher* 1,2, Xiao Rong Zeng1,2, Zachary Barnes1, Silvina Levis1,2 and Nancy G Klimas* 1,2 1Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL USA 2Miami Veterans Health Care Centre, 1201 NW 16th St, Miami, FL USA

Maybe professor Edwards can explain these fluctuations of cytokine?

I have a question for professor Edward: can cytokines flair up or go down by both mental- or physical stress (running)?
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I agree this is not a paradigmn change and I doubt it will lead to a biomarker (I think Schutzer's study is much more encouraging).
Could you explain a bit more the type of inconsistency shown with cytokine measurements? How do you account for the difference between groups if the measurements are "inconsistent"?
 
C

charles shepherd

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The following researchers have shared their thoughts on this research with us.

Prof Julia Newton, Clinical Professor of Ageing and Medicine and Dean of Clinical Medicine, School of Clinical Medical Sciences, Newcastle University

“From the perspective of a CFS/M.E. researcher I would consider this to be a very important study from a group who are known to be preeminent in their field. The cohort is large, the patients included well characterised and consistently phenotyped. The authors highlight the limitations of some of the previous literature in terms of the heterogenous nature of this patient group and how this can lead to issues when drawing conclusions about the significance of a study’s findings. To address this they have therefore stratified the patients in their study in a physiologically meaningful way according to length of disease.

“I would consider that this study is an exciting step forward in this historically challenging field. What are now needed is confirmatory studies performed in other centres using equally stringent characterisation of the study group. If we can encourage research in this area it could have the real potential for the development of novel therapies (or the repurposing of existing treatments) that address the underlying biological mechanisms that lead to this terrible disease.”

Prof Jonathan Edwards, Professor Emeritus in Connective Tissue Medicine, Department of Medicine, University College London

“I think this study is an important step forward in trying to track the biological basis of M.E./CFS. It is perhaps a pity that media organisations and some responding colleagues have focused on headline aspects rather than detailed content. This is not a report of a diagnostic test, but it might help us get there. The study is important because it shows systematic differences in levels of cytokines measured in blood samples from people with early (<3 years) and later (>3 years) M.E./CFS.

“The sample size is large enough and the fact that the same pattern crops up time after time with many cytokines indicates that these are not chance findings. The main concern is for some systematic confounding factor in methodology or population differences.

“However, this is a concern for all M.E./CFS studies and the strengths of this study are that it makes use of a multicentre collaboration with well-standardised methodology and that a population-based confounder seems less likely within two cohorts differing only in disease duration rather than disease versus ‘healthy control’ (age differences seem unlikely to be critical).

“It illustrates the power of longitudinal analysis. The lack of correlation of cytokines with symptom severity also tends to increase their plausibility as markers of causal process rather than a secondary physiological state. Considering how difficult it has been to get high quality biological studies like this off the ground in M.E./CFS I think this is a major triumph.”
 
nandixon

nandixon

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cigana said:
I agree this is not a paradigmn change and I doubt it will lead to a biomarker (I think Schutzer's study is much more encouraging).
Could you explain a bit more the type of inconsistency shown with cytokine measurements? How do you account for the difference between groups if the measurements are "inconsistent"?
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That Schutzer study used the infamous Fukuda criteria for diagnosing "CFS," meaning that PEM was not a strict requirement, but rather an optional requirement. So it may be hard to say how useful the specific results from it are.

The methodology might otherwise be good though when PEM is required.
 
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aimossy

aimossy

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Should I put this here or a new thread. Doctor on Australia's TV channel 7 talks about the new findings and admits to previous perceptions ...almost. I appreciated the honesty.

Edit: Doctor Andrew Rochford.

 
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alex3619

alex3619

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cornwall13 said:
What does professor newton mean when she said "repurposing of existing treatments"?
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Many old drugs, including drugs that never made it to market, might be used to treat these issues. Such drugs have had much of the research already done, all that has to be done is test them out on a new disease or problem. This can save years on research time. It may also mean, if the drug is old enough, that it is CHEAP.

This can save years on bringing a drug to market, and if the drug has a very safe side effect record it might save a lot of years. In the best case it may mean the drug is available much sooner and at a very low price.

In the worst case, a new drug, from scratch, might take ten to twenty years to bring to market, has less understood side effects, and could mean you have to mortgage your house for just one course of treatment.
 
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