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Advances in understanding pathogenesis and developing new therapies are hastened by the use of effective animal models of disease. In inflammatory bowel disease, such as Crohn's disease, a variety of models have been used, including the IL-10 knockout mouse. However, in order to be truly valuable, the models need to respond to existing therapy in a way which resembles the human disease. In the light of recent developments, in which refractory Crohn's disease responds well to anti-TNF antibody therapy, we set out to validate the IL-10 knockout model of Crohn's disease by examining its response to anti-TNF therapy. We developed a new scoring system for IL-10 knockout mice, similar to the Crohn's Disease Activity Index in humans, analysed stool samples for cytokines and compared the findings with histology. We found that anti-TNF antibody therapy starting at 4 weeks markedly ameliorated the disease, as judged by the clinical score or by histological analysis of the gut. Furthermore, analysis of stool samples for cytokines revealed a marked diminution of inflammatory cytokines, adding a further accurate measure of the improvement. This model may thus be useful for evaluating other therapeutic modalities of relevance to Crohn's disease.

Original publication

DOI

10.1046/j.1365-2249.2003.02193.x

Type

Journal article

Journal

Clin Exp Immunol

Publication Date

07/2003

Volume

133

Pages

38 - 43

Keywords

Animals, Antibodies, Colitis, Crohn Disease, Cytokines, Feces, Immunization, Passive, Injections, Intraperitoneal, Interleukin-10, Intestines, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Tumor Necrosis Factor-alpha