Interleukin-12 induced interferon-gamma increases inflammation in acute dextran sulfate sodium induced colitis in mice.

There is increasing evidence that IL-12 and Th1-cytokines play an important role in intestinal inflammation. We therefore examined the role of IL-12 and interferon-gamma (IFN-gamma) in our model of dextran sulfate-induced acute colitis in mice. Treatment of mice with rmIL-12 during colitis induction resulted in severe aggravation as demonstrated by a greater loss of body weight, an increase of the histological parameters, and reduction of myeloperoxidase activity in colonic biopsies. Depletion of neutrophils in mice also led to aggravation of colitis. Neutralization of IFN-gamma in IL-12-treated mice with colitis inhibited these effects of IL-12. Neutralization of endogenous IFN-gamma or IL-12 with specific antibodies in DSS-treated mice, however, had only weak ameliorating effects. Since IL-12 and IFN-gamma have been shown to mediate experimental chronic colitis we conclude that the transition from a macrophage/neutrophil determined response to a Th-cell response promotes chronic intestinal inflammation.