Treatment of Relapsing Paralysis in Experimental Encephalomyelitis by Targeting Th1 Cells through Atorvastatin

摘要: Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, exhibit numerous functions related to inflammation, such MHC class II down-regulation, interference with T cell adhesion, and induction apoptosis. Here we demonstrate that both subcutaneous oral administration atorvastatin inhibit the development actively induced chronic experimental autoimmune encephalomyelitis in SJL/J mice significantly reduce inflammatory infiltration into central nervous system (CNS). When treatment was started after disease onset, reduced incidence relapses protected from further disability. Both autoreactive response measured by proliferation toward encephalitogenic peptide PLP139–151 cytokine profile indicate a potent blockade helper type 1 immune response. In vitro assays not only inhibited antigen-specific responses, but also decreased mediated direct TCR engagement independently LFA-1. Inhibition due apoptosis induction, linked negative regulation on cycle progression. However, early activation unaffected, reflected unaltered calcium fluxes. Thus, our results provide evidence for beneficial role statins attack CNS.