Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group Very interesting psoriasis drug in trials

This one basically stimulates IL 10 (an anti-inflammatory cytokine) Thus it uses the bodys own systems to shut down inflammation. It is a herbal drug from India. Psoriasis improvement scores are impressive in phase 2 trials.

http://abstract.mci-group.com/cgi-bin/mc...how&client=

Impressive results for a herbal med. Combining it with bile salt could be a very effective/cheap/safe treatment for psoriasis.

"A total of 800 psoriasis patients participated in the study and 551 were treated with oral bile acid (dehydrocholic acid) supplementation for 1-8 weeks...During this treatment, 434 patients (78.8%) became asymptomatic.
- http://www.ncbi.nlm.nih.gov/pubmed/14643904

Drizz - facinating. YOu always find new and great info. Thank you. Will be a bonus for those sffering from the dreaded psoriasis (TG mine is v.v. mild - don't need to do owt about it). But great find.

Kudos man -

Hi drizzit,

Here's a bit of background on IL-10 as it applies to AS.

IL-10 is a pleiotrophic cytokine produced predominantly by monocytes (and lesser Th2 cells, mast cells and Tregs. It functions to down regulate Th1 cytokines (IFN-gamma and TNFalpha), to suppress the presentation of MHC Class II antigens by APC’s, and co-stimulatory molecules on macrophages. It enhances B cell survival, proliferation and antibody production. It is an essential immune-regulator in the intestinal tract.

Interestingly, a 5-fold increase in the proportion of Treg cells is observed in the gut of AS patients as compared to healthy subjects with 70-80% of these cells also producing IL-10. Blocking IL-10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients. In conclusion, an active Treg cell response, mainly dominated by IL-10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.

David

So is the thought we are producing extra IL 10 via Treg Cells and the body is trying to quell the inflammation of AS? without the increased IL 10 production we would see significant Gut inflammation via TH 17?

that makes sense since we know IL 23 will induce IL 17/TH17 production and the body responds to the IL 23 with IL 10 to try and dampen the inflammation. hmmmm

I like this pic but IL 17 needs to be added. I think this research was before we separated IL 23 and IL 12

http://www.biocarta.com/pathfiles/h_il10pathway.asp

BTW david -- one of the reasons I am on LDN is a Doc that works with it reports an increase of IL 10 in many of her patients. I think anything anti-inflammatory is a good thing Interesting enough the LDN is performing very well in IBD trials at Penn State University

Drizzit,

That's exactly how I see it.
Many AS patients feel they don't have gut problems - but that's probably because they are having a good Treg response to mask the ileitis.

In patients with Inflammatory bowel disease perhaps the Treg response is depressed because of genetic factors.

Interesting also that probably the type of psoriasis related to AS is 'relatively' mild in AS patients because frank psoriasis is assocaited with HLA-Cw06 and most AS patients probably aren't 'lucky' enough to have this as well as B27 and the other AS-associated genes.

Skin cells when damaged or stressed release CCL20 (a chemoattractant for Th17 cells) and this might explain the Koebner effect and the association of psoriasis (all be it mild) with AS.

No doubt, someone will reply and say they have really severe psoriasis with AS ....

http://rheumatology.oxfordjournals.org/content/50/4/646.short

This paper discusses the plasticity seen between Th17 and Tregs.

Cheers David

So what is it that prevents IL 10 from preventing Bone, skin, and joint inflammation or is it just not as effective in those body areas as in the Gut. Perhaps those cells do not produce IL 10 to counter the IL 17/TH17 reaction.

Does increasing IL 10 help in some areas of the body but not others?

so many questions the deeper you go

Hi Drizzit,

Whilst there appears to be a strong Treg response in the ileum of AS patients this doesn't negate the effects on the peripheral joints and spine of having Th17 activation in the gut - aimed at resolving a perceived 'infection' by a Gram Negative bacteria (inferred Gram Negative because TLR4 and TLR5 are upregulated in AS).
The paper 'Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in Ankylosing Spondylitis' presents a plausible model that explains many of the aspects of AS.

KIR are a family of MHC class I-binding receptors expressed by NK and minor subsets of T cells (including Th17 cells). KIR3DL2 is three-Ig domaiin KIR whose cognate ligands include HLA-A3 and HLA-A11. Their studies have shown that KIR3DL2 does NOT recognize HLA-B27/Beta2-microglobulin/peptide heterotrimeric complexes but that they DO bind to B27 homodimers, which are expressed on T cells of AS patients.
They also showed that these KIR3DL2+ activated Th17 cells survive preferentially, thus build up in numbers, are attracted to area of stressed fibro-cartilage (in response to the chemoattract CCL20 which normally allows joint repair - homeostasis), and where they further attract effector cells such as macrophages that induce joint damage, enthesitis and the full effects of AS.