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A new animal model of post-surgical bowel inflammation and fibrosis: the effect of commensal microflora.
  1. Rachael J Rigby (rachael_rigby{at}med.unc.edu)
  1. University of North Carolina, United States
    1. Meagan R Hunt (meagan_hunt{at}med.unc.edu)
    1. University of North Carolina, United States
      1. Brooks P Scull (scull{at}email.unc.edu)
      1. University of North Carolina, United States
        1. James G Simmons
        1. University of North Carolina, United States
          1. Karen E Speck
          1. University of North Carolina, United States
            1. Michael A Helmrath (michael_helmrath{at}med.unc.edu)
            1. University of North Carolina, United States
              1. P Kay Lund (empk{at}med.unc.edu)
              1. University of North Carolina, United States

                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.

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