Simvastatin Reduces Expression of Cytokines Interleukin-6, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Circulating Monocytes From Hypercholesterolemic Patients

Abstract

Objective-A number of studies have shown that statins decrease morbidity and mortality in patients with cardiovascular diseases. The anti-inflammatory effects of statins have recently been implicated in the clinical benefit that can be obtained in the treatment of atherosclerosis. Little is known about the mechanisms by which statins counteract inflammation. Methods and Results-In this study, we asked whether simvastatin can influence in vitro and in vivo production of the proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. A total of 107 hypercholesterolemic patients were treated with simvastatin. As measured by ELISA, serum levels of cytokines significantly decreased after 6 weeks of treatment (PϽ0.05).

Direct Anti-Inflammatory Mechanisms Contribute to Attenuation of Experimental Allograft Arteriosclerosis by Statins

“…26 Several investigators demonstrated that high-dose statins inhibit MCP-1 expression by both ECs and macrophages. 27 By inhibiting L-mevalonate synthesis, statins prevent the synthesis of important downstream isoprenoid intermediates of the cholesterol biosynthetic pathway and block the modification of various regulatory proteins. 16,28 Because the inhibition of RANTES and MCP-1 production in vitro was reversed by administration of L-mevalonate, the statin effect may be due to a biosynthetic pathway that involves a mevalonate intermediate or could involve a mevalonatesensitive modification of proteins such as Ras, Rho, PI 3 kinase, or nitric oxide.…”

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

“…Fluvastatin, atorvastatin, cerivastatin, and simvastatin significantly decrease circulating MCP-1 levels in patients with hypercholesterolemia (58-61). Statins also decrease levels of the chemokine IL-8 (59,62), another important regulator of leukocyte adhesion and chemoattraction. Statin effects on these and other soluble mediators may therefore indirectly alter the conditions for leukocytes to migrate to sites of inflammation.…”

“…In separate, randomized prospective studies of patients with hypercholesterolemia and hypertension, treatment with simvastatin resulted in decreased circulating IL-1␤, and IL-1␤ production by isolated PBMCs, respectively (82,83). Both atorvastatin and simvastatin significantly decrease levels of circulating IL-6 and TNF␣, in addition to IL-1␤, in patients with hypercholesterolemia (39,41,59,84). Carotid plaques resected from patients taking statins contain significantly lower concentrations of IL-6 (P ϭ 396 ABELES AND PILLINGER 0.0005), suggesting that statins do, indeed, alter local inflammation in atherosclerotic lesions (85).…”

There Is No Evidence for an Increase in Acute Coronary Syndromes After Short-Term Abrupt Discontinuation of Statins in Stable Cardiac Patients

“…Endothelial dysfunction is also characterized by elevated levels of the vasoconstrictive substance endothelin-1, 13 and statins have also been shown to inhibit the expression of endothelin-1 in vascular endothelial cells. 14 In addition, statins have demonstrated the ability to inhibit platelet aggregation 15,16 and monocyte adhesion to the endothelial surface 17,18 and to possess antioxidant 19 and antiinflammatory activity, particularly the reduction in C-reactive protein levels. 20,21 Although some of these nonlipid effects may be operative even before substantial lipid benefits accrue, others may not be truly independent of lipid reduction.…”