Immunomodulatory and anti-inflammatory activities of statins.
The statins are a group of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used extensively in medical practice because of their ability to reduce cardiovascular mortality and stroke. Although this protective activity was initially ascribed to the inhibition of cholesterol biosynthesis in the liver, clinical trials and basic research studies indicate that, beyond their cholesterol-lowering activity, statins might affect the function of different cell types in extrahepatic tissues. Here we will review the different mechanisms by which the statins exert their immunomodulatory and anti-inflammatory functions. We propose that statin pleiotropism is a key to the explanation of these activities, as it enables statins to act cooperatively in various steps of the inflammatory reaction, including terminal differentiation of immune cells, endothelial cell function, and regulation of the molecules that steer these cells to the sites at which they exert their immunomodulatory activity.
Mira
Emilia
E
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain.
Mañes
Santos
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017951:Antigen Presentation / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D018925:Chemokines / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors