Effects and mechanism of action of immunomodulating agents against schistosomiasis-induced hepatic inflammation and fibrosis in mice

While hepatic schistosomiasis results in morbidity from infection and complications of liver fibrosis, there are few medicines/means available to prevent, control, or treat this fibrosis. The aim of this study was to assess the potential beneficial effects of immunomodulating agents against hepatic schistosomal fibrosis. Swiss mice were infected with Schistosoma mansoni live cercariae and then left untreated or administered praziquantel (500 mg/kg/d), rosiglitazone (4 mg/kg/d), propolis (250 mg/kg/d), bisphenol A diglycidyl ether (BADGE) (30 mg/kg/d), or a combination of praziquantel + propolis, praziquantel + rosiglitazone, praziquantel + BADGE, or rosiglitazone + BADGE. Blood samples were collected at various time points post-infection to determine serum interleukin (IL)-2 and IL-10, and IgE and IgG levels, as well as those of alanine and aspartate aminotransferases (ALT and AST). Liver and intestine were recovered at 8 and 12 weeks post-infection, the liver was assessed for hepatic hydroxyproline content and, as with the colon samples, underwent immunohistochemical examination to assess tissue egg count. The results indicate that serum IL-2 levels were significantly increased in infected mice treated with praziquantel and praziquantel + propolis, praziquantel + rosiglitazone, or praziquantel + BADGE (each compared to infected-only hosts), but decreased in infected mice that received rosiglita-zone alone. Serum IL-10 levels were significantly decreased in all drug-treated infected mice except those that received rosiglitazone, treatment with BADGE alone caused no change. Serum IgE, IgG, ALT, AST and hepatic hydroxyproline levels were significantly decreased in all drug-treated infected mice except for those that received BADGE alone (no change). From these results, we conclude that combination of chemotherapy plus immunomodulating agents modulate cellular and humoral immune responses and that this leads to significant reductions in hepatic hydroxyproline build-up/liver pathologies associated with schistosomiasis.   Key words: Schistosoma mansoni, hepatic fibrosis, praziquantel, rosiglitazone, propolis.