HMG-CoA reductase inhibitor attenuates experimental autoimmune myocarditis through inhibition of T cell activation

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Abstract
Objective: This study tested the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor affects T cell-mediated autoimmunity through inhibition of nuclear factor-κB (NFκB) and reduces the severity of experimental autoimmune myocarditis (EAM). Methods: EAM was induced in Lewis rats by immunization with myosin. High-dose or low-dose fluvastatin or vehicle was administered orally for 3 weeks to rats with EAM. Results: Fluvastatin reduced the pathophysiological severity of myocarditis. Fluvastatin inhibited expression of NFκB in the nuclei of myocardium in EAM. Fluvastatin reduced production of Th1-type cytokines, including interferon (IFN)-γ and interleukin (IL)-2, and inhibited expression of inflammatory cytokine mRNAs in the myocardium. Infiltration of CD4-positive T cells into the myocardium and T cell proliferative responses were suppressed by fluvastatin. Plasma lipid levels did not differ between the groups. Conclusions: Fluvastatin ameliorates EAM by inhibiting T cell responses and suppressing Th1-type and inflammatory cytokines via inactivation of nuclear factor-κB, and this activity is independent of cholesterol reduction.

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