Regulation of Liver Fibrosis during Murine Schistosomiasis Mansoni

Abstract

Background: The main pathology of Schistosoma mansoni (S. mansoni) infection is induced by a granulomatous tissue reaction against the parasite eggs. Unfortunately, no therapy has been proven to prevent the progression of hepatic fibrosis associated with granulomatous hypersensitivity to parasite eggs. Accumulating evidence has demonstrated a critical pathogenic role for both interleukin 17 (IL-17) and interleukin 13 (IL-13) in organ fibrosis. Objective: The present study investigated the role of IL-17 and IL-13 in the pathogenesis of liver fibrosis during S. mansoni infection. Material and Methods: Thirty female C57BL/6 mice were divided into three groups, normal, infected, and anti- mouse IL-17 treated groups. The infected and anti-mouse IL-17 groups were infected with 40±5 cercariae of S. mansoni per mouse. Neutralizing rat anti-mouse IL-17 mAb or an isotype-matched rat IgG mAb was first administered intraperitoneally 3 weeks after S. mansoni infection (62.5μg per mouse) then at the same dose every third day until 2 days before killing. Serum IL-17, IL-13, and proinflammatory cytokines levels were determined by ELISA. Liver granulomas were measured by an ocular micrometer. Results: Serum level of IL-17 was significantly higher in infected mice compared with non-infected animals. Reducing IL-17 activity using anti-IL-17 monoclonal antibodies improves liver functions and reduces the size of the liver granulomas. Meanwhile, Th-2 profibrogenic cytokine IL-13 was also decreased in infected/anti-IL-17 mAB- treated mice. IL-17-induced proinflammatory mediators (IL-1Land TNF-that involved in liver fibrosis were markedly reduced in anti-IL-17 mAB-treated mice. Conclusion: IL-17 and IL-13 contribute to granulomatous inflammatory and fibrosing reactions in murine schistosomiasis.