Cholesterol-lowering statins possess anti-inflammatory activity that might be useful for treatment of MS

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce atherogenesis and cardiovascular morbidity. These effects are attributed to alteration in cholesterol metabolism and reduction in low-density lipoprotein (LDL) formation. Now there is evidence that statins have immunomodulatory activities that could be beneficial in treatment of various inflammatory conditions. In 1995, pravastatin was reported to reduce hemodynamically significant rejection episodes and increase survival in cardiac transplant recipients, independent of its cholesterol-lowering effects.1 This observation prompted subsequent in vitro studies that demonstrated that statins interfered with production of several important proinflammatory mediators.2,3⇓ Of relevance to treatment of CNS inflammatory conditions such as MS, lovastatin suppressed production of inducible nitric oxide synthase (iNOS) and secretion of tumor necrosis factor-α (TNFα) by interferon-γ (IFNγ)-activated astrocytes and microglia.2 iNOS and TNFα may play important roles in the inflammatory process of MS.4 Lovastatin partially suppressed acute experimental autoimmune encephalomyelitis (EAE) in rats.5 Central in importance to activation of proinflammatory CD4 T cells, statins inhibited IFNγ-inducible major histocompatibility complex (MHC) class II upregulation on certain antigen-presenting cells via inhibition …