Usefulness of CD4+CD45RBhigh CD25- cell-transferred SCID mice for preclinical evaluation of drugs for inflammatory bowel disease.

Abstract

Mouse colitis induced by transfer of CD4+CD45RBhigh CD25- cells share many pathological features with human inflammatory bowel disease (IBD). However, there is little known about how mouse colitis responds to drugs used for IBD treatment. To address this issue, we have investigated the effects of the IBD drugs, dexamethasone and anti-tumor necrosis factor-alpha antibody, on the mouse experimental colitis. Administration of either drug ameliorated their morbid signs such as body weight loss, colon shortening, and an increased ratio between colon and body weights (C/B ratio). Also improved were mucosal inflammatory signs in the colon, and histological damage scores were significantly decreased. Of the proinflammatory cytokines assayed in colon and plasma samples from the colitis mice, the colonic interleukin (IL)-1beta level alone was significantly decreased by either drug administration. Regression analysis of data obtained with either drug revealed a close correlation between the histological damage score and C/B ratio or colonic IL-1beta level. The present results show that the experimental mouse colitis responds to IBD drugs with its amelioration and that the C/B ratio and colonic IL-1beta are available as a disease marker for IBD, suggesting the usefulness of this mouse model of colitis for pre-clinical screening of drug candidates for IBD treatment.