Effects of simvastatin on human T cells in vivo

Atherosclerosis. 2007 Jul;193(1):186-92. doi: 10.1016/j.atherosclerosis.2006.06.022. Epub 2006 Jul 24.

Abstract

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 Th1 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins / blood
  • C-Reactive Protein / metabolism
  • Concanavalin A / pharmacology
  • Double-Blind Method
  • Enterotoxins / pharmacology
  • HLA-DR Antigens / blood
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / immunology
  • Interleukin-2 Receptor alpha Subunit / blood
  • L-Selectin / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Simvastatin / pharmacology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Apolipoproteins
  • Enterotoxins
  • HLA-DR Antigens
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-2 Receptor alpha Subunit
  • Lipids
  • Concanavalin A
  • L-Selectin
  • enterotoxin B, staphylococcal
  • C-Reactive Protein
  • Simvastatin