Protection Against Schistosomiasis-Induced Hepatic Fibrosis By Modulating The Immune System

Objectives: Hepatic Schistosomiasis resulted in the morbidity from infection due to its complications of liver fibrosis. However, there are few medicines or means avai lable to contro l and t reat f ibrosis in Schistosomiasis. The aim of this study was to assess the beneficial effects of immunomodulating agents in hepatic schistosomal fibrosis. Methods: Three hundred male Swiss albino mice infected with Schistosoma mansoni live cercariae were divided into seven groups: Control; infected (Schistosoma mansoni live cercariae); Praziquantel (500 mg/kg/day); Rosiglitazone (4 mg/kg/day); Propolis (250 mg/kg/day); Bisphenol A diglycidyl ether (BADGE) (30 mg/kg/day); combination of Praziquantel plus Propolis, Praziquantel plus Rosiglitazone, Praziquantel plus BADGE, Rosiglitazone plus BADGE. Blood samples, Liver and intestine were taken for determination of serum interleukin-2, interleukin-10, immunoglobulin E and G, Alanine aminotransferas, Aspartate aminotransferase, hepatic hydroxyproline, immunohistochemical examination of liver tissues and tissue egg count (in liver and colon). RESULTS: Serum level of IL-2 showed significant increase in mice treated with Praziquantel and Praziquantel plus Propolis, plus Rosiglitazone or plus BADGE and decrease in Rosiglitazone group. Serum IL-10 showed significant decrease in all treated groups except Rosiglitazone and BADGE showed no significant change. Serum IL-10 showed significant decrease in all treated groups except Rosiglitazone and BADGE showed no significant change. Serum IgE, IgG, ALT, AST and hepatic hydroxyproline, showed significant decrease in all treated groups except BADGE showed no significant change. Conclusions: We can concluded that combination of chemotherapy plus immunomodulating agents modulate cellular and humoral immune responses led to significant reduction in hepatic hydroxyproline content and liver pathology in schistosomal infected mice. Introduction Schistosomiasis is one of the most important public health problems affecting Egyptians, especially the rural inhabitants of the Nile Delta [1]. Praziquantel has become the drug of choice against Schistosomiasis. Indeed, it has effectively become the only antischistosomal drug that is commercially available. Praziquantel has activity against all schistosome species with minimal adverse effects, and it is also effective against other trematode and cestode infections [2]. Eggs of Schistosoma mansoni embolize to liver, where the granulomatous inflammatory response induces presinusoidal inflammation and periportal fibrosis. T cells and B cells have also been implicated as playing a regulatory role in schistosome granuloma formation [3]. Hepatic fibrosis, a precursor of liver cirrhosis, is a consequence of severe liver damage that occur in many patients with chronic disease and involves the abnormal accumulation of extracellular matrix (ECM) and hepatic stellate cells (HSCs) [4]. HSCs, is the central event in hepatic fibrogenesis, can undergo the p rocess o f ac t i va t ion and transdifferentiate to a myofibroblast-like phenotype characterized by an increase in cell proliferation, loss of vitamin A-storing capability, expression of αSMA ( α-smooth muscle actin) and overproduction of ECM components, especially type I collagen [5]. Peroxisome proliferator activated receptor γ (PPARγ) activation has been found to affect diverse physiological and pathophysiological events, including stimulation of adipocyte differentiation, regulation of lipid metabolism, inhibition of cell proliferation and induction of apoptosis [6]. Propolis also exhibits anti-inflammatory effects against acute and chronic models of inf lammation (formaldehyde-and adjuvant-induced arthritis, carrageenan-and prostaglandin (PGE)-induced paw oedema, cotton pallet granuloma). The exact mechanism of the anti-inflammatory actions of propolis is still unclear [7]. Among the compounds tested, only caffeic acid phenethyl ester (CAPE) and galangin contributed to the anti-inflammatory activity of propolis; however, the contribution of CAPE was greater. Propolis also exhibits immunostimulatory and immunomodulatory WebmedCentral > Research articles Page 2 of 18 WMC001498 Downloaded from http://www.webmedcentral. com on 28-Dec-2011, 12:48:16 PM effects in vitro on macrophages, while in vivo it increases the ratio of CD4 and CD8 cells in mice [8]. AIM OF THE WORK The aim of this study was to assess the possible disturbance in the immune system and mechanism through which immunomodulating agents can produce their beneficial effects in Schistosomiasis induced hepatic fibrosis.