Suppressive effect of non-anaphylactogenic anti-IgE antibody on the development of dextran sulfate sodium-induced colitis.

Inflammatory bowel disease (IBD) is a spectrum of immune-mediated chronic disorders of the intestine. Patients with IBD tend to exhibit significantly elevated levels of IgE in their serum. In general, the pathogenesis of IBD exhibits inflammatory events such as immunoglobulin E (IgE)-mediated hypersensitivity. We examined the effect of the non-anaphylactogenic anti-IgE antibody, which has been known to block IgE functions, in an animal model of ulcerative colitis induced by the oral intake of dextran sulfate sodium (DSS) for seven days. The non-anaphylactogenic anti-IgE antibody was subcutaneously injected on day 0 of DSS treatment. The disease activity index (DAI) was calculated by scoring intestinal states, including body weight loss, diarrhea, and rectal bleeding, and the activities of myeloperoxidase (MPO) and chymase were measured in the colon tissue. In addition, the expression of tumor necrosis factor (TNF)-alpha and cyclooxygenase (COX)-2 was determined by Western blotting. Administration of the anti-IgE antibody markedly reduced the histological damage to the colon and the DAI increment exhibited by the DSS-induced colitis. The anti-IgE antibody also significantly suppressed the activities of MPO and chymase as well as the expression of TNF-alpha and COX-2 in the DSS-treated colon tissue. Furthermore, the elevation of IgE levels in serum was induced by DSS and reduced by anti-IgE antibody injection. Thus, these results indicate that the IgE response played an important role in the clinical signs and the expression of inflammatory mediators in a colitis model caused by DSS treatment, suggesting that the non-anaphylactogenic anti-IgE antibody may be a useful therapeutic agent for ulcerative colitis.