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P014. Pharmacological evaluation of the SCID T cell transfer model of colitis

T. Holm1, S. Poulsen2, H. Markholst1, S. Reedtz-Runge1

1Novo Nordisk, Immunopharmacology, Maaloev, Denmark; 2University of Copenhagen, Department of medical anatomy, Copenhagen, Denmark

Background: Animal models are important for preclinical evaluation of new drug candidates against the Inflammatory Bowel Diseases (IBD): Crohn's Disease and Ulcerative Colitis. A number of marketed drugs are efficacious in man and thus it seems important to validate the efficacy of these drugs in the animal models as well to further dissect how well the model reflect the human disease and response to therapy.

Methods: Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently used IBD drugs and IBD drug candidates i.e. anti-TNF‑a, TNFR-Fc, anti-IL‑12p40, anti-IL‑6, CTLA4-Ig, anti-a4b7 integrin, enrofloxacin/metronidazole and cyclosporine.

Results: We found that anti-TNF‑a, antibiotics, anti-IL‑12p40, anti-a4b7 integrin, CTLA4-Ig, and anti-IL‑6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. Furthermore, of perhaps even further interest, antibiotics, anti-IL‑12p40 and CTLA4-Ig induced remission when administered to animals with established disease, whereas the other compounds did not.

Conclusions: The data suggest that the adoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. However, the finding that some well established IBD therapeutics is not efficacious in the model, highlights important differences between the experimental model and the human disease.