Abstract
Pleiotropic effects are now described for the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (or statins) that might have utility in the context of chronic inflammatory autoimmune disease. Here we discuss the pharmacology and established uses of statins and in this context describe potential anti-inflammatory and immune-modulatory effects. An extensive in vitro data set defines roles for statins in modifying endothelial function, particularly with respect to adhesion molecule expression and apoptosis. Broader effects on leukocyte function have now emerged including altered adhesion molecule expression, cytokine and chemokine release and modulation of development of adaptive immune responses via altered MHC class II upregulation. In vivo data in several inflammatory models, including collagen-induced inflammatory arthritis and experimental autoimmune encephalomyelitis, suggest that such effects might have immune-modulatory potential. Finally, a recent clinical trial has demonstrated immunomodulatory effects for statins in patients with rheumatoid arthritis. Together with their known vasculoprotective effects, this growing body of evidence provides compelling support for longer-term trials of statin therapy in human disease such as rheumatoid arthritis.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Anticholesteremic Agents / pharmacology
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Anticholesteremic Agents / therapeutic use
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Apoptosis / drug effects
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Arthritis, Experimental / drug therapy
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Arthritis, Rheumatoid / drug therapy*
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Autoimmune Diseases / drug therapy*
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Cell Adhesion Molecules / metabolism
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Chemokines / metabolism
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Clinical Trials as Topic
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Cytokines / metabolism
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Double-Blind Method
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Drug Evaluation, Preclinical
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Edema / chemically induced
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Edema / drug therapy
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Graft Rejection / prevention & control
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
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Immunologic Factors / pharmacology*
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Immunologic Factors / therapeutic use
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Inflammation / drug therapy*
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Kidney Transplantation
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Mice
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Molecular Structure
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Monocytes / drug effects
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Monocytes / metabolism
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Multicenter Studies as Topic
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Randomized Controlled Trials as Topic
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Rats
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Anticholesteremic Agents
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Cell Adhesion Molecules
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Chemokines
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Cytokines
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Immunologic Factors