Journal Article

Aggravation of Established Colitis in Specific Pathogen-free IL-10 Knockout Mice by Restraint Stress Is Not Mediated by Increased Colonic Permeability

Michael Schultz, Chuan Chuan Lai, Anna Lisa Lindstroem, Kathy Stein, Glen Donaldson, Mark Thompson-Fawcett and A. Grant Butt

in Journal of Crohn's and Colitis

Published on behalf of European Crohn's and Colitis Organisation

Volume 9, issue 9, pages 754-762
Published in print September 2015 | ISSN: 1873-9946
Published online June 2015 | e-ISSN: 1876-4479 | DOI: https://dx.doi.org/10.1093/ecco-jcc/jjv098
Aggravation of Established Colitis in Specific Pathogen-free IL-10 Knockout Mice by Restraint Stress Is Not Mediated by Increased Colonic Permeability

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  • Medicine and Health
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  • Gastro-intestinal and Colorectal Surgery
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Background:

Pathogenic mechanisms responsible for the undulating symptom pattern, or indeed causative agents for the development, of inflammatory bowel diseases [IBD] are largely unknown. Many physicians and most patients are convinced that stress affects the course of IBD. As with most factors that contribute to IBD, it is unclear whether stress merely exacerbates established disease or indeed contributes to the development of disease. We designed this study to investigate whether stress induces or aggravates colitis in interkeukin-10 knockout [IL-10 ko] mice and to determine the role of intestinal permeability in this model of stress-related colitis.

Methods:

The study was divided into two experiments depending on the age of the animals. Stress was induced by placing 5-week old disease-free mice or 8-week-old mice (IL-10ko and wild type [wt]) with mild colitis in movement restrainers for 2h twice daily for 7 days. The development of colitis was assessed clinically [weight and faecal pellet production], histologically [haematoxylin and eosin staining], and biochemically [colonic IL-2, IL-4, IL-6, IL-12p40, TNFα, and IFNγ]. Permeability was measured in Ussing chambers.

Results:

Faecal pellet production increased significantly in all stressed animals compared with control animals, indicating successful application of stress. Stressed 8-week old mice lost weight [p < 0.001] and stressed IL-10-/- mice showed a significantly increased histological score compared with non-stressed or wt mice [p < 0.001]. There was no appreciable difference in cytokine production. Stress did not alter intestinal permeability.

Conclusions:

Restraint stress aggravates experimental colitis in 8-week old IL-10ko mice but cannot induce colitis in disease-free younger mice. This is not mediated by an increased intestinal permeability.

Keywords: Inflammatory bowel disease; animal model; IL-10 knockout mouse; restraint stress

Journal Article.  6187 words.  Illustrated.

Subjects: Medicine and Health ; Clinical Medicine ; Gastroenterology ; Gastro-intestinal and Colorectal Surgery ; Health, Illness, and Medicine

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