Effect of Simvastatin on Treatment of Experimental Autoimmune Encephalomyelitis through Immunomodulating Response

Studies indicate that simvastatin decrease brain lesions and symptoms in patients with multiple sclerosis. The aim of the present study was to investigate the effect of simvastatin on treatment of experimental autoimmune encephalomyelitis (EAE) as an animal model for multiple sclerosis. Male C57BL/6 mice were placed in two therapeutic groups. EAE was induced by immunization of mice with MOG35-55 peptide and complete Freund's adjuvant. Treatment with oral simvastatin (1 mg/kg/day) was started on day 3 before the immunization until 25 days after immunization. Non-treated EAE mice received phosphate buffer alone with the same schedule. Leukocyte infiltration into the brain, proliferation of spleen mononuclear cells and interferon-gamma (IFN-γ) and interleukin-10 (IL-10) production from cultured spleen supernatants and clinical score of disease were determined. Clinical score and onset of EAE, number of infiltrating cells in the brain and cell proliferation in EAE-treated mice were significantly less than those in the non-treated EAE (control) mice (P=0.01). There was no difference between simvastatin and control group with regard to the level of IFN-γ production. However, IL-10 production was significantly enhanced in the spleen mononuclear cells in the treated EAE group compared with that in the non-treated EAE group (P=0.008). Treatment with simvastatin ameliorated the EAE by inducing Th2 cytokine (IL-10) and reducing the proliferation and infiltration of leukocytes into the brain of EAE mice. Therefore, simvastatin treatment may be effective in MS patients by immunomodulating of the immune response.