Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin

Proinflammatory cytokines and inducible nitric oxide synthase (iNOS) are in volved in the pathogenesis of experimental allergic encephalomyelitis (EAE) , an animal model of multiple sclerosis (MS). We have previously reported t hat lovastatin (Pahan, K., Sheikh., F.G., Namboodiri, A. and Singh, I., Lov astatin and Phenylacetate inhibit the induction of nitric oxide synthase an d cytokines in rat primary astrocytes, microglia and macrophages. J. Clin. Invest., 100 (1997) 2671-2679.), an inhibitor of the mevalonate pathway, in hibits the expression of iNOS and proinflammatory cytokines in rat primary glial cells (astroglia and microglia) and macrophages. The present study un derlines the therapeutic importance of lovastatin in ameliorating the neuro inflammatory disease process in the central nervous system of EAE rats. Imm unohistochemical results show a higher degree of expression of iNOS, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in brain s of rats with acute monophasic EAE relative to the control animals. Admini stration of lovastatin inhibited the expression of iNOS, TNF-alpha and IFN- gamma in the CNS of EAE rats and improved the clinical signs of EAE suggest ing that this compound may have therapeutic potential in the treatment of n euroinflammatory diseases like MS. (C) 1999 Elsevier Science Ireland Ltd. A ll rights reserved.