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 TNFΔare/+ mouse.

METHODS:

Thirty-six, 6-weeks-old TNFΔare/+ 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 TNFΔare/+ 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 TNFΔare/+ 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.

• Authors: Ioannis Georgopoulos, Eleftheria Mavrigiannaki, Sotiria Stasinopoulou, Georgios Renieris, Georgios Nikolakis, Giorgos Bamias, Dina Tiniakos, Ioannis Papaconstantinou
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 67 Issue 5 Pg. 1783-1793 (05 2022) ISSN: 1573-2568 [Electronic] United States
• PMID: 34350516 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Tumor Necrosis Factor-alpha

Topics

• Animals
• Constriction, Pathologic
• Crohn Disease (pathology)
• Humans
• Ileitis (pathology)
• Inflammation
• Intestinal Obstruction (etiology)
• Mice
• Tumor Necrosis Factor-alpha (genetics, metabolism)