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Journal of Crohn's and Colitis: 9 (7)

Editor-in-Chief

Laurence J. Egan, Ireland

Associate Editors

Maria T. Abreu, USAShomron Ben-Horin, IsraelSilvio Danese, ItalyPeter Lakatos, HungaryMiles Parkes, UKGijs van den Brink, NLSéverine Vermeire, Belgium

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Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse — A model mimicking inflammatory bowel disease

Kristine Holgersen , Peter Helding Kvist , Helle Markholst , Axel Kornerup Hansen , Thomas Lindebo Holm
DOI: http://dx.doi.org/10.1016/j.crohns.2013.08.002 147-160 First published online: 1 February 2014

Abstract

Background In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified.

Aim To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies.

Methods The PAC IL-10 k.o. model was established on a C57BL/6 J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed.

Results The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model.

Conclusion The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research.

Keywords
  • Inflammatory bowel disease
  • Crohn's disease
  • Interleukin-10 knock out mouse
  • Piroxicam
  • Abbreviations
    COX
    cyclooxygenase
    IL-10 k.o
    interleukin-10 knock out
    mAb
    monoclonal antibody
    Meics
    murine endoscopic index of colitis severity
    NSAID
    non-steroidal anti-inflammatory drug
    PAC
    piroxicam-accelerated colitis
    WT
    wild type
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