The complement and contact systems may be involved in the pathophysiological process of inflammatory bowel disease (IBD). C1 inhibitor (C1INH) is the most important inhibitor of both the complement and contact systems. We evaluated the role of these systems and the effect of both active and inactive forms of C1INH (iC1INH) in dextran sulfate sodium (DSS)-induced colitis mouse model. Three percent DSS was used in drinking water to induce colitis in complement C3-deficient (C3−/−) mice, bradykinin type 2 receptor deficient (Bk2R−/−) mice, and C57BL/6 mice. After ten days DSS exposure, C3−/− mice exhibited markedly less weight loss than wild-type (WT) mice (12 ± 3.3% vs. 30 ± 1.2%, P < 0.05) and developed a milder disease-activity index (DAI), histological score, colon shortening, and myeloperoxidase (MPO) elevation ( P < 0.05, respectively). The Bk2R−/− mice were not protected from the disease. Seven-day treatment with either native C1INH or iC1INH reduced the severity of the disease in WT mice, as indicated by decreased weight loss (15 ± 1.8%, 14 ± 2.1% vs. 30 ± 1.2%, P < 0.05, respectively), DAI, intestinal tissue damage, and MPO elevation compared with untreated WT DSS control mice ( P < 0.05, respectively). These findings suggest that complement plays a role in the development of DSS-induced colitis and that blockade of the complement system might be useful for the acute phase of IBD treatment. C1INH, however, leads to an amelioration of DSS-induced colitis via a mechanism that does not involve the inhibition of complement or contact system activation but does result in significant suppression of leukocyte infiltration.
Role of TNFR-related 2 mediated immune responses in dextran sulfate sodium-induced inflammatory bowel disease