Increased IL-13 may lead to fibrosis in Crohn's Disease

[David]

Abstract
Background

Fibrosis is a serious consequence of Crohn’s disease (CD), often necessitating surgical resection. We examined the hypothesis that IL-13 may promote collagen accumulation within the CD muscle microenvironment.
Methods

Factors potentially modulating collagen deposition were examined in intestinal tissue samples from fibrotic (f) CD and compared with cancer control (C), ulcerative colitis (UC) and uninvolved (u) CD. Mechanisms attributable to IL-13 were analysed using cell lines derived from uninvolved muscle tissue and tissue explants.
Results

In fCD muscle extracts, collagen synthesis was significantly increased compared to other groups, but MMP-2 was not co-ordinately increased. IL-13 transcripts were highest in fCD muscle compared to muscle from other groups. IL-13 receptor (R) α1 was expressed by intestinal muscle smooth muscle, nerve and KIR+ cells. Fibroblasts from intestinal muscle expressed Rα1, phosphorylated STAT6 in response to IL-13, and subsequently down-regulated MMP-2 and TNF-α-induced MMP-1 and MMP-9 synthesis. Cells with the phenotype KIR+CD45+CD56+/−CD3− were significantly increased in fCD muscle compared to all other groups, expressed Rα1 and membrane IL-13, and transcribed high levels of IL-13. In explanted CD muscle, these cells did not phosphorylate STAT6 in response to exogenous IL-13.
Conclusions

The data indicate that in fibrotic intestinal muscle of Crohn’s patients, the IL-13 pathway is stimulated, involving a novel population of infiltrating IL-13Rα1+, KIR+ innate lymphoid cells, producing IL-13 which inhibits fibroblast MMP synthesis. Consequently, matrix degradation is down-regulated and this leads to excessive collagen deposition.

Source

 

[David]

I've read that Infliximab can actually lead to fibrosis as it helps heal. Sure enough, Infliximab doesn't reduce IL-13 concentrations.

Guess what DOES reduce IL-13 concentrations? Naltrexone.

 

[kiny]

I think they should just find a way to reduce collagen content.

There's lots of stuff that reduces TGF-beta 1 and IL-13 but too much of it and with any wound you will bleed like a pig, it could end up killing people during perforations. Not to mention that it ends up increasing fibrosis instead of reducing it. Things like resveratrol reduce TGF and IL-13, but many people have said they bleed much longer while taking it.

I think they should just let the wounds heal without trying to interfere with them because you need the exact balance of TGF-beta 1, IL-13, duration etc, to get a proper wound healed, medication is too inprecise, they should find a way to fix collagen deposition after the event, which I think is easier and much safer.