Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis

T Scheinin, DM Butler, F Salway… - Clinical & …, 2003 - academic.oup.com
T Scheinin, DM Butler, F Salway, B Scallon, M Feldmann
Clinical & Experimental Immunology, 2003academic.oup.com
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 …
Summary
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.
Oxford University Press