Ellagic acid reduces murine schistosomiasis mansoni immunopathology via up-regulation of IL-10 and down-modulation of pro-inflammatory cytokines production

Abstract

Context: The main immunopathology in schistosomiasis mansoni consists of a granulomatous inflammatory and fibrosing reaction in the liver and intestine against tissue trapped parasite eggs, which is mediated by CD4+ T cells. Ellagic acid (EA), a natural phenolic compound found in fruits and nuts, has potent anti-oxidant and anti-inflammatory properties.Objective: The aim of the present study was to evaluate the potential effect of EA in the treatment of murine schistosomiasis mansoni and its induced immunopathology.Materials and methods: Mice were infected, each with 40 Schistosoma mansoni (S. mansoni) cercariae and treated with EA at a total dose of 600 mg/kg body weight. At week eight of infection, mice were sacrificed; worm and egg burden were estimated; hepatic granuloma volume and collagen fibers deposition were evaluated; splenocytes were prepared and cultured in the presence of S. mansoni antigens.Results: EA treatment did not show any significant effect on worm or egg burden. However, hepatic granuloma volume and collagen fibers deposition were largely reduced with EA treatment. EA treatment augmented specific IL-10 production in response to S. mansoni antigenic stimulation. However, specific IL-1β, IL-4, IL-12, IL-13, IL-17A, TNF-α and IFN-γ production were significantly reduced with ex vivo and in vivo EA treatment. Serum IgM and IgG levels significantly increased, whereas specific IgA and IgE levels did not significantly change with EA treatment.Conclusion: EA treatment modulates cellular and humoral immune responses of infected mice and leads to a significant reduction of liver pathology in acute murine schistosomiasis mansoni.