Differential dose effects of recombinant IL-25 on the development of dextran sulfate sodium-induced colitis

We evaluated different dose effects of rIL-25 on acute ulcerative colitis. Mice were fed 2.5% dextran sulfate sodium (DSS) for 5 days while infused i.p. with repeated doses of rIL-25 (0.2, 0.4 and 0.8 mu g) in PBS or PBS only after every 24 h at the same time as the start of the DSS exposure. Clinical, macroscopical and microscopical assessment of colitis severity with survival study was performed. Colonic IL-25 expression and production of IFN-gamma, IL-10 and IL-4 was also analyzed. At a dose of 0.2 mu g, colitis was aggravated with high mortality, better improvements were observed at a dose of 0.4 mu g, and colitis-induced diarrhea was reversed at a dose of 0.8 mu g. The expression of IL-25 was found to decrease in severe colitis. Moreover, IL-25 inhibited production of mucosal IFN-gamma, induced increase in IL-10 but not IL-4. Improvements in DSS-induced colitis in response to IL-25 suggest IL-25's protective role by mechanisms including inhibition of IFN-gamma with enhancement of anti-inflammatory release.