Abstract

Objective: Ileo-cecal resection (ICR) is common in Crohn’s disease (CD). Inflammation and fibrosis frequently recur at the site of anastomosis or in the small intestine (SI). No animal models of post-surgical inflammation and fibrosis exist. We developed a model of ICR in IL-10 null and wild-type (WT) mice to test the hypothesis that that ICR promotes post-surgical inflammation and fibrosis in SI or anastomosis of genetically susceptible IL-10 null, but not WT or germ free (GF)-IL-10 null mice.

Design: GF-IL-10 null mice were conventionalized (CONV) and 3 weeks later randomized to ICR, transection (T) or no treatment (NoTx). Age-matched conventionally raised (CONV) WT and GF-IL-10 null mice received ICR, T or NoTx. Animals were killed 28 days later.

Main outcome measures: Histological scoring, real-time PCR for TNFα and collagen, and immunostaining for CD3+ T cells, assessed inflammation and fibrosis.

Results: After ICR, CONV-IL-10 null, but not CONV-WT mice, developed significant inflammation and fibrosis in SI and inflammation in anastomosis compared to NoTx or T controls. Fibrosis occurred in anastomosis of both CONV-IL-10 null and CONV-WT following ICR. GF-IL-10 null mice developed little or no inflammation or fibrosis in SI or anastomosis after ICR.

Conclusions: ICR in CONV-IL-10 null mice provides a new animal model of post-surgical inflammation and fibrosis in SI and anastomosis. Absence of inflammation and fibrosis in SI of CONV-WT and GF-IL-10 null following ICR indicates that post-surgical small bowel disease occurs only in genetically susceptible IL-10 null mice and is bacteria dependent.