Experimental Intestinal Stenosis Alters Crohn's Disease-Like Intestinal
Inflammation in Ileitis-Prone Mice
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Abstract
Background Clinical observations indicate that mechanical factors
contribute to the expression or recurrence of Crohn's disease. We
investigated whether the creation of an intestinal stenosis could alter
the severity of the expected Crohn-like ileitis, in a Crohn's disease
animal model, the TNF Delta are/+ mouse. Methods Thirty-six, 6-weeks-old
TNF Delta are/+ mice, were divided into 3 intervention groups: triple
suture, single suture and sham. In the terminal ileum, in the first
group, a triple suture stenosis was created, whereas, in the second, a
loose suture was placed. Same triple-suture stenosis was performed on
twelve wild type mice. All animals were sacrificed at 6 weeks
post-operatively and the ileum parts were evaluated histopathologically.
A summative total ileitis score was applied in each sample using a
bespoke semiquantitative histological scoring system for the Crohn-like
changes. Results The triple suture stenosis induced significant muscular
hypertrophy proximal to interventional site which was more prominent in
TNF Delta are/+ than wild type mice. In triple suture group, the total
ileitis score was significantly increased proximal to the intervention
as compared to the single suture (P: 0.004) and the sham groups (P:
0.013). The total ileitis score distally, was unaffected, regardless of
the experimental intervention. Intestinal stenosis did not induce
intestinal inflammation in wild type mice. Conclusion The creation of a
stenosis in the terminal ileum of TNF Delta are/+ mice alters Crohn-like
inflammation. We assume that mechanical forces, such as intraluminal
pressure, may contribute as important co-factors to the pathophysiology
of Crohn's disease in genetically predisposed subjects