Experimental Intestinal Stenosis Alters Crohn’s Disease-Like Intestinal Inflammation in Ileitis-Prone Mice

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 Δare/+ mouse. Methods: Thirty-six, 6-weeks-old TNF Δare/+ 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 Δare/+ 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 WT mice. Conclusions: The creation of a stenosis in the terminal ileum of TNF Δare/+ 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.

Experimental Animal Models for Studying Intestinal Obstruction

“…The authors of this chapter encountered all the difficulties of designing a research protocol for experimental IO. Georgopoulos et al [8] based on clinical observation, aimed to test the never-before-proven hypothesis that the expression or recurrence of Crohn's disease in humans is related to narrow intestinal passings such as valves, strictures, or tight anastomoses. To prove this hypothesis, the authors set up an experimental research protocol using knock-in mice that combined partial intestinal obstruction and genetic predisposition in Crohn-like disease.…”

No Longer Stretching Credibility: Mechanical Force Meets Inflammation in Experimental Intestinal Stenosis

“…To explore this phenomenon, Georgopoulos et al [7] in this issue of Digestive Diseases and Sciences created an experimental intestinal ileal stenosis through an intestinal suturing method [8] in the well-characterized TNFΔARE spontaneous ileitis model. The experiments were controlled by a sham operation with a suture not causing stenosis, as well as a sham operation with no suture.…”