Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice

Abstract

The hygiene hypothesis suggests an inverse relationship between the incidence of parasitic infections and chronic inflammatory bowel diseases (IBD). We investigated the therapeutic potential of Schistosoma mansoni and Ancylostoma caninum soluble proteins on experimental colitis in mice. Colitis was induced by intrarectal administration of 10 mg trinitrobenzene sulfonic acid (TNBS) in 30% ethanol. Six hours after TNBS injection, mice were treated intraperitoneally with helminth proteins. Three days later, colonic inflammation was scored based on 5 inflammatory parameters: clinical disease activity, macroscopic and microscopic inflammation score, extent of inflammation, and myeloperoxidase (MPO) activity. To determine immunological pathways induced by S. mansoni proteins we measured cytokine profiles of T-lymphocytes from colon, mesenteric lymph nodes (MLN), and spleen by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Control mice showed no signs of inflammation, whereas all inflammatory parameters were significantly increased in mice with colitis. Treatment of mice with colitis with S. mansoni or A. caninum proteins decreased the macroscopic inflammation score, extent of inflammation, and MPO activity. Immunologically, induction of colitis significantly increased expression of IFN-gamma mRNA in the inflamed colon. Treatment with S. mansoni proteins caused a decrease of proinflammatory cytokines (IFN-gamma, IL-17) in colon and MLN, whereas the production of regulatory cytokines (IL-10, TGF-beta) increased significantly in colon tissue. Treatment with proteins of S. mansoni and A. caninum ameliorated TNBS-induced colitis in mice. S. mansoni proteins increased mRNA expression of regulatory cytokines while suppressing expression of proinflammatory cytokines. Therefore, we suggest a therapeutic potential for helminth proteins in the treatment of IBD.