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Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
...but there is an interesting parallel to be drawn between the results of this cross-sectional study and the (initial, unpublished) results coming from the longitudinal study currently underway at the Younger Lab. They too are finding a correlation between certain cytokines and severity of symptoms, and again finding that whilst this correlation exists the actual cytokine levels on average are within normal tolerances. This seems consistent to me and if the case would indicate that cytokines drive the disease but it would appear that there is some kind of abnormal response to these cytokines or that the cytokines are correlated with another disease process that is doing the actual damage..

Exactly. 'Within normal parameters' suggests the problem may lie with signalling/receptors or some other immune signal associated with 'inflammation'.
 

Londinium

Senior Member
Messages
178
But is their grouping by severity planed or a post-hoc thing. If it is post-hoc how many other ways of looking at the data did they find until the hit on this one?

Agreed, which is why my first concern was around this. Correcting for FDR is a base requirement IMHO but is not sufficient in and of itself.

However, grouping by severity looks to my untrained eye as being one of the first ways one would split the data rather than some of the other studies like the one (Peterson?) that only got to statistical significance by creating a whole new category of 'atypical' that included such gems as 'got it on holiday' (I paraphrase, but only just). Correlating by severity is analogous to doing a dose-response curve so doesn't feel like the data has been tortured too much to give p<0.05. It's also consistent with previous and upcoming longitudinal findings so I think it's worth giving the benefit of the doubt.
 

msf

Senior Member
Messages
3,650
I think it´s quite likely that cytokine levels are depressed from where they ´should´ be, i.e. patient´s immune systems adapt to the constant stimulation of higher levels of LPS by downregulating inflammatory cytokines, but in severely ill patients the levels of LPS are so high (as reported by KDM, who first reported the raised levels of LPS established by Hanson) that even with the downregulation the levels of inflammatory cytokines are still above controls. As I suggested in my blog, I think research will eventually show that measuring both these factors after exercise will show a much clearer separation between patients and controls.
 

msf

Senior Member
Messages
3,650
Exactly. 'Within normal parameters' suggests the problem may lie with signalling/receptors or some other immune signal associated with 'inflammation'.

So, does anyone know of other immune signals that are associated with inflammation?
 
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Gijs

Senior Member
Messages
690
Cytokines will not bring a valid test for ME/CFS. These finding(s), like TGF B is well known for more than decades. They found it in 1991. Sorry for Stanford, but their findings are useless for a diagnostic test at his point.
 
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Gijs

Senior Member
Messages
690
Gijs, can you tell us a piece of research that you were enthusiastic about?

Yes, there are more....

Brain Res. 1999 Nov 6;846(2):145-53
Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance to central fatigue
Inoue K, Yamazaki H, Manabe Y, Fukuda C, Hanai K, Fushiki T
Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan


Physiol Behav. 1998 May;64(2):185-90
Release of a substance that suppresses spontaneous motor activity in the brain by physical exercise
Inoue K, Yamazaki H, Manabe Y, Fukuda C, Fushiki T
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan

This one is even from 1991...

Cytokine (1991) 3: 292-8
Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the Chronic Fatigue Syndrome
Chao CC, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK
Department of Medicine, Hennepin County Medical Centre, Minneapolis, MN 55415
 

Wonkmonk

Senior Member
Messages
1,006
Location
Germany
Sorry for Stanford, but their findings are useless for a diagnostic test at his point.

But even if they are, the fact that it was published in a journal like PNAS and the media echo it has created will do a lot of good. Many more people will now have heard of the disease and hopefully at least some will take it more seriously.

Thank you, Dr Montoya (et al.) :thumbsup:
 

msf

Senior Member
Messages
3,650
Yes, there are more....

Brain Res. 1999 Nov 6;846(2):145-53
Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance to central fatigue
Inoue K, Yamazaki H, Manabe Y, Fukuda C, Hanai K, Fushiki T
Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan


Physiol Behav. 1998 May;64(2):185-90
Release of a substance that suppresses spontaneous motor activity in the brain by physical exercise
Inoue K, Yamazaki H, Manabe Y, Fukuda C, Fushiki T
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan

This one is even from 1991...

Cytokine (1991) 3: 292-8
Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the Chronic Fatigue Syndrome
Chao CC, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK
Department of Medicine, Hennepin County Medical Centre, Minneapolis, MN 55415

One from the 21st century?
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
I think it´s quite likely that cytokine levels are depressed from where they ´should´ be, i.e. patient´s immune systems adapt to the constant stimulation of higher levels of LPS by downregulating inflammatory cytokines, but in severely ill patients the levels of LPS are so high (as reported by KDM, who first reported the raised levels of LPS established by Hanson) that even with the downregulation the levels of inflammatory cytokines are still above controls. As I suggested in my blog, I think research will eventually show that measuring both these factors after exercise will show a much clearer separation between patients and controls.

Those are very interesting points! The other thing I wonder about is the uniqueness of each persons micro-biome and therefore the unique set of toxins, from the different pathogenic bacteria, on each persons immune system, getting into the bloodstream.

Would all the different toxins, endotoxins and exotoxins, cause the same immune response in every person? I don't really know but my guess would be probably not.

That could lead to different cytokine profiles in many, if not all and therefore no clear consistent findings in these cytokine studies.

Jim