Beneficial role of simvastatin in experimental autoimmune myositis

Abstract

ObjectiveStatins have immunomodulatory potential in autoimmune diseases but had not been studied as a disease-modifying agent in inflammatory myopathies. The objective of this study is to assess the effect of simvastatin in an experimental model of autoimmune myositis in mice on muscle strength and histopathology. MethodsFour groups of mice (n = 5 per group) were selected for experimentally induced myositis. Mice were immunized with 1.5 mg myosin in complete Freund’s adjuvant weekly for two times and injected with 500 ng pertussis toxin twice immediately after each immunization. From day 1 before immunization to 10 days after the last immunization, mice were treated with oral simvastatin (10 or 20 or 40 mg/kg) diluted in DMSO. The control group mice were injected with complete Freund’s adjuvant weekly for two times and did not receive treatment. Non-immunized mice (n = 5 per group) were treated either with simvastatin (5 mg/kg or 20 mg/kg or 40 mg/kg of simvastatin diluted in DMSO) or with DMSO. ResultsInflammation was observed in myositis groups with positive myositis-specific antibodies. Muscle strength dropped significantly after immunization. Immunized simvastatin 20 mg/kg treated group had significantly higher muscle strength versus non-treated myositis mice and versus other simvastatin doses. Besides, a trend toward higher serum Th17 percentage population was found in immunized non-treated mice, versus immunized simvastatin- treated mice, without significant difference. ConclusionSimvastatin at 20 mg/kg decreases the severity of myositis in experimental autoimmune myositis and is a candidate of being a disease-modifying agent in inflammatory myopathies.