Immunomodulatory effects of 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, potential therapy for relapsing remitting multiple sclerosis.

ABSTRACT

This study characterized immunomodulatory targets of statins in humans and their potential for treatment of relapsing remitting multiple sclerosis (RR MS). Statins inhibited the proliferative response of mononuclear cells. Simvastatin, the statin with the strongest antiproliferative effect, inhibited IFN-gamma-induced expression of MHC class II DR on monocytes and decreased their antigen presenting capacity. As for T lymphocytes, it inhibited their activation and expression of the Th1 lineage differentiation markers. Simvastatin inhibited IFN-gamma, TNF-alpha, and IL-2 secretion, as well as the expression of T-bet, a transcription factor that regulates Th1 cell differentiation.