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

Background: Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Dis ruption of the IL-10 gene in C57/Black6 mice results in enterocolitis in th e presence of intestinal bacteria. This study investigated gut mucosal barr ier function sequentially during the development of colitis in this model. Methods: Animals were bred in specific pathogen-free conditions and transfe rred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 1 2, 14 and 15 weeks of age. Barrier function was assessed by measuring intes tinal 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 End oCAb. The HIS correlated positively with both intestinal permeability and I gM and IgG EndoCAb. Intestinal permeability showed a positive correlation w ith EndoCAb. Conclusion: IL-10 knockout mice develop colitis with an associated disturba nce in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL-10 knockout mouse shares thes e histological, physiological and biochemical features with human inflammat ory bowel disease and is therefore suitable for therapeutic trials. A measu re of endotoxaemia correlated directly with intestinal permeability in this model.