Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium-induced colitis in mice

OBJECTIVE: Helminth immunomodulation in the host has been shown to have therapeutic implications in inflammatory bowel diseases. In this study we aimed to evaluate the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in a dose-dependent manner on dextran sulfate sodium (DSS)induced colitis in mice. METHODS: The anti-inflammatory activity of rBmCys on mice peritoneal exudate cells was initially analyzed in vitro. BALB/c mice were fed with 5% DSS for 7 days to induce colitis. The colitis mice were treated intraperitoneally with rBmCys (10, 25 or 50 mu g for the three different groups of mice) on days 1, 3 and 5 of the DSS administration. Disease severity was assessed by the disease activity index (DAI) and macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Cytokine profiles were measured in sera and cultured splenocytes of treated mice followed by stimulation with rBmCys. RESULTS: rBmCys showed anti-inflammatory activity in vitro. Treatment of DSS-induced colitis with rBmCys in mice ameliorated the overall disease severity as reflected by a significant reduction in weight loss, the DAI, mucosal edema, colon damage and myeloperoxidase activity of the colonic mucosa. While the mRNA expressions of IFN-beta, TNF-alpha, interleukin (IL)-5, IL-6 and IL-17 were downregulated, IL-10 expression was upregulated in the splenocytes of colitis mice treated with rBmCys. The amelioration of DSS-induced colitis occurred in a dose-dependent manner. CONCLUSION: The results of this study indicate an anti-inflammatory potential of rBmCys and provide evidence for using this protein as a promising therapeutic agent in ulcerative colitis.