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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e128.)
© 2006 American Heart Association, Inc.

Letters to the Editor

Letter to the Editor

Modulation of Toll-Like Receptor Expression: A Further Effect of Statins?

José C. Alves-Filho; Fernando Q. Cunha

Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

Inhibitors of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (or statins) represent a family of chemically related molecules selected for their lipid-lowering effect. Statins are extensively used in medical practice, and large clinical trials have demonstrated that this class of lipid-lowering drugs greatly reduces cardiovascular-related morbidity and mortality in patients with and without coronary disease.¹ However, benefits from statin therapy appear to exceed their lipid-lowering effect.

We have read with great interest the article by Methe and colleagues² published in Arteriosclerosis, Thrombosis, and Vascular Biology. The investigators described that statin (simvastatin and atorvastatin) treatment reduces Toll-like receptor 4 (TLR4) surface expression on human monocytes in vivo and in vitro in a dose-dependent fashion. Although the mechanisms of immunomodulatory properties of statins have not been fully clarified, the authors make the interesting observation that the effects of statins on reduction of TLR4 surface expression were correlated with downregulation of IRAK-1 kinase activity and reduced expression of proinflammatory cytokines after stimulation with lipopolysaccharide (LPS), suggesting that expressional regulation of Toll-like receptors is controlled by proinflammatory cytokine production. In accordance, recently, Niessner and colleagues³ demonstrated that high-dose simvastatin pretreatment blunted TLR2 and TLR4 surface expression on monocytes in a human endotoxemia model. Moreover, the reduction of TLR expression also was associated with diminished tumor necrosis factor (TNF)- and monocyte chemoattractant protein-1 (MCP-1) plasma levels. Altogether, these findings suggest that the effect of statins on TLR expression may reveal a potential mechanism for their beneficial statin effects not only in cardiovascular disease . . . [Full Text of this Article]