TNF targeting small molecule attenuates colonic inflammation in acute DSS-induced colitis mice

Abstract Background Inflammatory bowel disease (IBD) is a chronic and multifactorial inflammatory disorder which is comprising Crohn’s disease (CD) and ulcerative colitis (UC). Although the incidence of IBD has steady increase in worldwide, the conventional drug therapies with 5-aminosalicylates, corticosteroids, and immunosuppressants are insufficient to maintain remission and can occur side effects. Therefore, other class of drug therapies using specific cytokine inhibitor have recently been focused. In this study, we aimed to investigate that anti-inflammatory effects of TNF targeting small molecule in dextran sodium sulfate (DSS)-induced colitis model. Methods C57BL/6 (21–23g) mice were administered 2–2.5% DSS in the drinking water for 5 days to induce acute colitis. Different doses of IA-14069 (20, 40, 80, 160 mg/kg) were orally treated daily for 5–12 days and the mice were sacrificed for the experiments. Normal or DSS control group was given drinking water only or DSS only. Disease severity, body weight change, and colon length were measured, and serum levels of TNF, IFN-g, IL-6, IL-17 and IL-5 were analyzed by ELISA. Colonic epithelial damage was observed by H&E staining of colon tissue. Results Compared with normal group, oral administration of 80 mg/kg IA-14069 significantly inhibited the severity of colitis, loss of body weight, and colon shortening of the DSS-induced colitis mice. Moreover, mucosal damages and production of the proinflammatory cytokines were markedly suppressed by treatment of IA-14069. Conclusion These findings suggest that IA-14069, a TNF-targeting small molecule, exerts a suppressive effect on DSS-induced colitis and may be used as an IBD therapeutic agent.