Statins as potential therapeutic agents in neuroinflammatory disorders

Olaf Stüve, Sawsan Youssef, Lawrence Steinman, Scott S. Zamvil

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Purpose of review: 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. Recent findings: 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 TH2 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. Summary: 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.

Original languageEnglish (US)
Pages (from-to)393-401
Number of pages9
JournalCurrent Opinion in Neurology
Volume16
Issue number3
DOIs
StatePublished - Jun 2003

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Multiple Sclerosis
Central Nervous System
Therapeutics
Stroke
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Central Nervous System Diseases
Demyelinating Diseases
Amyloid
Neurodegenerative Diseases
Cerebrospinal Fluid
Alzheimer Disease
Oxidoreductases
Nitric Oxide
Leukocytes
Anti-Inflammatory Agents
Animal Models
Tumor Necrosis Factor-alpha
Cholesterol

Keywords

  • Alzheimer's disease
  • Experimental autoimmune encephalomyelitis
  • HMG CoA reductase inhibitors
  • Ischemic stroke
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Statins as potential therapeutic agents in neuroinflammatory disorders. / Stüve, Olaf; Youssef, Sawsan; Steinman, Lawrence; Zamvil, Scott S.

In: Current Opinion in Neurology, Vol. 16, No. 3, 06.2003, p. 393-401.

Research output: Contribution to journalArticle

Stüve, Olaf ; Youssef, Sawsan ; Steinman, Lawrence ; Zamvil, Scott S. / Statins as potential therapeutic agents in neuroinflammatory disorders. In: Current Opinion in Neurology. 2003 ; Vol. 16, No. 3. pp. 393-401.
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