Interleukin 10‐deficient colitis: new similarities to human inflammatory bowel disease

RJ Kennedy, M Hoper, K Deodhar… - British journal of …, 2000 - Wiley Online Library
RJ Kennedy, M Hoper, K Deodhar, PJ Erwin, SJ Kirk, KR Gardiner
British journal of surgery, 2000Wiley Online Library
Background Interleukin (IL) 10 is a potent anti‐inflammatory cytokine. Disruption of the IL‐10
gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This
study investigated gut mucosal barrier function sequentially during the development of colitis
in this model. Methods Animals were bred in specific pathogen‐free conditions and
transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and
15 weeks of age. Barrier function was assessed by measuring intestinal permeability and …
Background
Interleukin (IL) 10 is a potent anti‐inflammatory cytokine. Disruption of the IL‐10 gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this model.
Methods
Animals were bred in specific pathogen‐free conditions and transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and 15 weeks of age. Barrier function was assessed by measuring intestinal permeability and antibody response to systemic endotoxaemia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (HIS) was calculated.
Results
The HIS increased progressively until 12 weeks, with an associated increase in intestinal permeability, and immunoglobulin (Ig) M and IgG EndoCAb. The HIS correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb.
Conclusion
IL‐10 knockout mice develop colitis with an associated disturbance in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL‐10 knockout mouse shares these histological, physiological and biochemical features with human inflammatory bowel disease and is therefore suitable for therapeutic trials. A measure of endotoxaemia correlated directly with intestinal permeability in this model. © 2000 British Journal of Surgery Society Ltd
Wiley Online Library