Statins as potential therapeutic agents in neuroinflammatory disorders.
OBJECTIVE
Multiple sclerosis is a central nervous system inflammatory demyelinating disease that is thought to have an autoimmune pathogenesis. Recent results indicate that 'statins', 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, which are the most commonly used oral cholesterol-lowering drugs, have immunomodulatory properties. In this article we will review those findings that indicate that statins may be beneficial in the treatment of multiple sclerosis, neurodegenerative disease, and ischemic stroke.


RESULTS
It was reported that statin treatment could either inhibit or reverse chronic and relapsing experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Several immunomodulatory properties of statins may account for their beneficial clinical effect: Statins decreased the migration of leukocytes into the central nervous system, inhibited MHC class II and costimulatory signals required for activation of proinflammatory T cells, induced a T(H)2 phenotype in T cells, and decreased the expression of inflammatory mediators in the central nervous system, including nitric oxide and tumor necrosis factor alpha. It was also demonstrated that statin use significantly reduced beta-amyloid secretion in the cerebrospinal fluid of experimental animals. Clinically, there is emerging evidence that statins have beneficial effects in patients with multiple sclerosis, Alzheimer's disease, and ischemic stroke.


CONCLUSIONS
In-vitro studies have indicated that statins may have anti-inflammatory properties. Results from in-vivo animal models suggest that statins may be beneficial in treatment of different central nervous system conditions. Larger scale, randomized, double-blind trials are needed to validate the role of statins as a treatment of inflammatory central nervous system diseases.
Stüve
Olaf
O
Department of Neurology, University of California, San Francisco, California 94143, USA.
Youssef
Sawsan
S
Steinman
Lawrence
L
Zamvil
Scott S
SS
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D007962:Leukocytes / Q000187:drug effects; D009103:Multiple Sclerosis / Q000188:drug therapy*; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D020521:Stroke / Q000188:drug therapy*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors