Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin.
Proinflammatory cytokines and inducible nitric oxide synthase (iNOS) are involved in the pathogenesis of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We have previously reported that lovastatin (Pahan, K., Sheikh., F.G., Namboodiri, A. and Singh, I., Lovastatin and Phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia and macrophages. J. Clin. Invest., 100 (1997) 2671-2679.), an inhibitor of the mevalonate pathway, inhibits the expression of iNOS and proinflammatory cytokines in rat primary glial cells (astroglia and microglia) and macrophages. The present study underlines the therapeutic importance of lovastatin in ameliorating the neuroinflammatory disease process in the central nervous system of EAE rats. Immunohistochemical results show a higher degree of expression of iNOS, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in brains of rats with acute monophasic EAE relative to the control animals. Administration 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 suggesting that this compound may have therapeutic potential in the treatment of neuroinflammatory diseases like MS.
Stanislaus
R
R
Department of Pediatrics, Medical University of South Carolina, Charleston, USA.
Pahan
K
K
Singh
A K
AK
Singh
I
I
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D008148:Lovastatin / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008148:Lovastatin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat