4.6 Article

Effects of simvastatin on human T cells in vivo

Journal

ATHEROSCLEROSIS
Volume 193, Issue 1, Pages 186-192

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2006.06.022

Keywords

atherosclerosis; inflammation; T cell; HMG-CoA reductase inhibitor

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Objective: The use of statins has shown several anti-inflammatory actions, including modulatory effects on T cells in vitro. Since the effects on human T cells in vivo are less clarified, our aim was to investigate the effects of simvastatin on human T cells in vivo and ex vivo. Methods and results: A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. The serum levels of C-reactive protein (CRP) were significantly reduced by simvastatin. The proportions of CD4+ and CD8+ T cell subsets expressing early (CD25) or late (HLA-DR) activation markers, as assessed by flow cytometry, were not changed by simvastatin. However, simvastatin tended to increase the density of HLA-DR and L-selectin per CD8+ T cell. The T helper(h) 1 /Th2 response was evaluated by stimulatory assays followed by intra-cellular staining of interferon-gamma and interleukin-4. Simvastatin treatment did not affect the Th 1 response but the results indicated a potential to suppress Th2. Conclusion: Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. However, the findings do not provide evidence that simvastatin-induced anti-inflammatory actions are related to any significant modulatory effects on human T cells in clinically healthy men with hypercholesterolemia. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

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