Mechanisms for the anti-inflammatory effects of statins.

PURPOSE OF REVIEW: Statins have diverse effects on the cellular mediators of inflammation and immunity that may be partially responsible for their efficacy in preventing cardiovascular disease, and which have encouraged their use in treating immune/inflammatory diseases. We discuss a selection of recently published studies that provide new insights into the mechanisms by which statins exert anti-inflammatory effects. RECENT FINDINGS: Statins have a variety of direct effects on the gene expression and function of cells of both the innate and adaptive immune systems, including endothelial cells, macrophages, dendritic cells and T cells. Many of these effects are related to statin blockade of GTPase isoprenylation, as has been shown in older literature, although newly identified cell type-specific downstream pathways of GTPase have been described. Recently published analyses of data from clinical trials have also provided further evidence that statin therapy has anti-inflammatory effects and benefits independent of lowering cholesterol. SUMMARY: Ongoing research continues to strengthen the case that statins can modulate immune responses by several mechanisms, independent of lowering blood cholesterol. A major challenge for investigators will be to determine how to take advantage of these new mechanistic insights to improve treatment of cardiovascular disease and primary immune/inflammatory disorders.