title: Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis.
abstract: 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.
authors.affiliation: Fourth Department of Surgery, University of Helsinki, Helsinki, Finland. tom.scheinin@hus.fi
authors.forename: T
authors.initials: T
authors.lastname: Scheinin
authors.forename: D M
authors.initials: DM
authors.lastname: Butler
authors.forename: F
authors.initials: F
authors.lastname: Salway
authors.forename: B
authors.initials: B
authors.lastname: Scallon
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000627:therapeutic use; D003092:Colitis / Q000473:pathology / Q000628:therapy; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000032:analysis; D005243:Feces / Q000737:chemistry; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000235:genetics*; D007422:Intestines / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000906:Antibodies; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10