Cytokines in the Cerebrospinal Fluids of Patients with CFS/ME

[Jon_Tradicionali]

There is. Look at Figure 1b from that study and the box labeled "IL10":

http://www.nature.com/mp/journal/vaop/ncurrent/fig_tab/mp201529f1.html#figure-title

Right. Was not mentioned on abstract so I assumed there was no significant finding.

 

[Snow Leopard]

You might be confusing CSF results with serum results?

I don't really think the CSF cytokine studies really indicate anything in particular.

 

[Jon_Tradicionali]

You might be confusing CSF results with serum results?

I don't really think the CSF cytokine studies really indicate anything in particular.

Sorry, who are you directing ?

 

[nandixon]

@Jon_Tradicionali

This 2011/2012 study by Light, et al., did show increased IL10 gene expression (i.e., increased IL10 mRNA levels) in ME/CFS patients upon exercise:

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome

Also interesting was their finding of decreased expression (upon exercise) for the adrenergic alpha 2A receptor gene (i.e., ADRA2A) in a smaller subgroup of ME/CFS patients. (This smaller subgroup did not show an increase in IL10 gene expression.) A history of orthostatic intolerance (OI) was significantly more common in this subgroup.

Note: There is an old thread on this paper here, but the possible significance of the work wasn't thoroughly discussed there at the time.

 

[Jon_Tradicionali]

@nandixon

Yes that doesn't surprise me at all. Quite clearly shows which genes are expressed during symptom flare(SF)/PEM. This is most important as it shows what is happening in the body during PEM which was not necessarily happening before.

Just a few quotes from the Lights study you have linked:

"These indicate strong positive relationships between post exercise pain and fatigue and increases in P2X4, TRPV1, α-2A, β-2, and IL10."

"Among the array of immune markers that we used for this gene expression profile, only the anti-inflammatory cytokine IL10 differed between patients and controls."

As I've mentioned before, iL-10 is a critical piece of the "puzzle", if not THE critical piece. It has been researched in the case of more "serious" viral infections such as HIV-1 and HEPC and found to facilitate viral persistence, surely the link isn't so difficult to make with ME/CFS considering the long history of viral persistence theories/findings.

I'll discuss one more study which explains this in detail and looks into iL-10 as a therapeutic target for vaccines in regards to clearing persistant viral infections. I'll do that once I get home from work though.

 

[Jon_Tradicionali]

@nandixon
Just a recent study which links intestinal bacteria (Lipkin) with il-10 through Bcell secretion(FlugeMella). Il-10 is designed to inhibit immune inflammatory response, but in doing so, it also inhibits the immune system from clearing the precise infection which triggered it in the first place.

Modifying small white blood cells may help treat immune disorders
Posted in: Medical Science News | Medical Research News | Medical Condition News

Published on June 16, 2015 at 2:57 AM

Modifying the small white blood cells that protect against disease might help treat immune disorders, according to a study published in Cellular and Molecular Gastroenterology and Hepatology, the basic science journal of the American Gastroenterological Association. Specifically, researchers found that modulation of B lymphocyte function may be a means of regulating T lymphocyte function to treat immune-mediated disorders, including inflammatory bowel diseases (IBD).

Researchers uncovered the following pathway: gut bacteria stimulate intestinal B lymphocytes to release interleukin (IL)-10 that, in turn, induces development of regulatory T lymphocytes that prevent excessive inflammatory responses and limit immune-mediated disease. This signaling depends, in part, on IL-27, a member of the IL-12 cytokine family that has been linked to IBD.

"Our study elucidates previously unexplored intercellular signals by which gut microbiota regulate the mucosal immune system to prevent disease," said lead study author Yoshiyuki Mishima, MD, PhD, University of North Carolina, Chapel Hill. "These findings potentially could be exploited to treat patients with IBD."

The role of B lymphocytes in producing protective antibodies that are secreted into the intestine is well-recognized. However, the contributions of B lymphocytes and their secreted products (other than antibodies) are not well understood. This mouse study shows that IL-10 and IL-27, which are secreted by B lymphocytes, regulate development of regulatory T lymphocytes.

"The work provides new insight into mechanisms by which gut bacteria drive mucosal immune homeostasis," added Jerrold R. Turner, MD, PhD, AGAF, editor-in-chief, Cellular and Molecular Gastroenterology and Hepatology.

Source: American Gastroenterological Association

 

[nandixon]

Thanks @Jon_Tradicionali. Here's a PubMed link for the study being referred to in the article you found:

Resident bacteria-stimulated IL-10-secreting B cells ameliorate T cell-mediated colitis by inducing Tr-1 cells that require IL-27-signaling

The role of B lymphocytes in producing protective antibodies that are secreted into the intestine is well-recognized. However, the contributions of B lymphocytes and their secreted products (other than antibodies) are not well understood. This mouse study shows that IL-10 and IL-27, which are secreted by B lymphocytes, regulate development of regulatory T lymphocytes.

(Quote is from the article. Bold is mine.)

The article/study you found gives a good example of the sort of possibility I was referring to in the following post on another thread (bold added here):

So once the "bad" B cells have been (rapidly) depleted by rituximab, whether they're bad because they're ultimately leading to plasma cell autoantibody production, or bad because they're leading to increased Treg activity and causing excessive immunosuppression, the time frame is approximately the same for the dying off of either the affected plasma cells or the affected Tregs, as the case may be.

I definitely like the possibility that an elevation of IL-10, and also TGF-β, that has been found to happen post-exertionally in ME/CFS may be an indication that Tregs are likely to be detrimentally involved. (My understanding is that the anti-inflammatory cytokines IL-10 and TGF-β meditate the suppressive effects of Tregs, i.e., higher levels of those cytokines are associated with greater Treg activity.)

In particular, the phenomenon of PEM, the defining characteristic of ME/CFS, might be related to an increase in immune suppression mediated by Tregs. Whether the Tregs themselves are actually defective may be less likely, but even if they are not this disease may possibly be treatable by directly reducing either Treg numbers or activity - for the immune suppressed subset of us, that is.

(Additional considerations are that T cells/Tregs can also produce IL10 - this is not limited to B cells - and that there are several types of Tregs.)

 

[Snowdrop]

@A.B. I tried using the link to the study you provided in your first post. It was broken (at least for me. I tried twice)
so I'm posting a new link here:
http://www.hindawi.com/journals/mi/2015/929720/