title: Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.
abstract: BACKGROUND
  Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear.
  
  
  METHODS
  To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA.
  
  
  RESULTS
  IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01).
  
  
  CONCLUSIONS
  Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.
authors.affiliation: Clinical Division of Cardiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Hannes Franz
authors.initials: HF
authors.lastname: Alber
authors.forename: Matthias
authors.initials: M
authors.lastname: Frick
authors.forename: Alois
authors.initials: A
authors.lastname: Suessenbacher
authors.forename: Jakob
authors.initials: J
authors.lastname: Doerler
authors.forename: Michael
authors.initials: M
authors.lastname: Schirmer
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Stocker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dichtl
authors.forename: Otmar
authors.initials: O
authors.lastname: Pachinger
authors.forename: Franz
authors.initials: F
authors.lastname: Weidinger
mesh_terms: D000069059:Atorvastatin; D023201:CD40 Ligand / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*
chemical_list: D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D023201:CD40 Ligand; D000069059:Atorvastatin