ABSTRACT
Experimental autoimmune myocarditis [EAM] is a well-established animal model for human autoimmune myocarditis and postmyocardilis dilated cardiomyopathv. Recently, independent of their anti-hyperlipidemic properties, statins have been categorized as new agents that ameliorate the course of several organspecific autoimmune inflammatory diseases. Thus, this study aimed to assess the possible immunoinflammatory suppressive potentiality of simvastatin therapy on EAM. Three groups of male Wistar rats were investigated in this study: Normal control group, untreated-EAM and simvastatin- treated EAM, EAM was induced by subcutaneous immunization with porcine cardiac myosin at days, 0 and 7. Simvastatin [10 mg/kg per day] was administered orally for 20 days. On day 21, the hearts were dissected out, weighed, and prepared for histological and immunohistochemical examinations. To evaluate the effects of simvastatin therapy on production of T helper type-1 [Th1], proinflammatory cytokines: tumor necrosis factor- alpha [TNF-alpha] and interferon- gamma [IFN-gamma], and the plasma cholesterol levels were measured at days 11 and 21 in all groups. Daily administration of simvastatin to rats with EAM efficiently suppressed myocarditis development, its histopathological severity, and macrophages infiltration [ED1+ Cells] and other mononuclear cells into hearts. The treated rats had significantly decreased heart weight and heart weight/body weight ratio [Hw/Bw] compared with untreated animals. The up-regulated serum levels of TNF-alpha and IFN gamma during the course of EAM were promptly down-regulated by simvastatin therapy. Plasma cholesterol levels did not differ between the groups. Our data reveal that chronic therapy with simvastatin potentially ameliorated EAM via inhibition of Th1 proinflammatory cytokine production and macrophage infiltration, and this activity is independent on cholesterol reduction. Furthermore, we anticipate that simvastatin could be a new immunotherdpeutic tool for autoimmune myocarditis and other cardiac autoimmune impairments