PACAP provides colonic protection against dextran sodium sulfate induced colitis.

Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a crucial role in immunity and inflammation. Our aim was to obtain insight in the role of PACAP in experimental colitis in mice and thus its possible role in inflammatory bowel disease. PACAP-deficient (PACAP-/-) mice and wild-type control mice were challenged by colitis-inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and difference of cytokine production in the proximal and distal colon. After DSS administration, mortality was more severe in PACAP-/- mice versus wild-type control mice. The histological score and the disease activity index of PACAP-/- mice were significantly higher than those of wild-type control mice. In proximal colon, production of IL-1beta and IL-6 in PACAP-/- mice were significantly upregulated on day 8 after DSS administration, compared to wild-type control mice. In distal colon, furthermore, production of IFNgamma, IL-1beta, IL-6, IL-12, and KC were significantly higher in PACAP-/- mice than in wild-type control mice on day 4. Our findings indicate that PACAP regulates the production of pro-inflammatory cytokine in the experimental colitis. (c) 2008 Wiley-Liss, Inc.