Downregulation of proinflammatory cytokines and dynamic expression of TGF-β1 molecules induced by anti-IL-17 mAb in murine schistosomiasis mansoni.

Abstract

Hepato-intestinal schistosomiasis is characterized by severe pathological changes at advanced chronic stages, including granulomatous lesions and liver fibrosis. The objective of our research was to assess the dynamic expression of profibrotic molecules, the transforming growth factor beta 1 (TGF-β1), and proinflammatory cytokines immunomodulation induced by interleukin 17 (IL-17) neutralization in murine Schistosomiasis mansoni. The study included 56 specific pathogen-free male C57BL/6 mice, divided into 3 main groups: GI uninfected normal controls, GII S. mansoni infected with 70±5 cercariae/non-treated, GIII S. mansoni infected and treated with anti-IL-17 monoclonal antibody (mAb), GIV S. mansoni infected and isotype-matched IgG2a mAb was given as a challenge. Mice were sacrificed at 6, 8, and 10 weeks after infection, then their liver enzymes and cytokines assessed, histopathological and immunohistochemical tested. The present study demonstrated a statistically significant elevation in serum levels of IL-17 (p < 0.01), TGF-β1 (p < 0.01), IL-1β (p≤0.001), IL-4 (p≤0.003), IL-6 (p≤0.05), and liver enzymes (ALT: p≤0.001; AST: p≤0.002). Additionally, granulomatous lesions and TGF-β1 expression were significantly increased (p < 0.001) in infected mice at 6, 8, and 10 weeks after infection. All showed significant reduction by neutralization with anti-IL-17 mAb. Finally, IL-17 exhibited potent profibrogenic activity, and anti-IL-17 mAb can be used to alleviate and counteract this impact in murine S. mansoni.