Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction

Clin Sci (Lond). 2009 Jan;116(1):45-52. doi: 10.1042/CS20080042.

Abstract

LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg x kg(-1) of body weight x day(-1) via oral gavage) starting on the first day after induction of MI. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10 protein, the TNF-alpha/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dt(max), +147%; and LV end-diastolic pressure, -27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-alpha, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-alpha/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin
  • Cytokines / blood
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Hemodynamics / drug effects
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation Mediators / blood
  • Interleukin-10 / blood*
  • Macrophages / pathology
  • Male
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Pyrroles / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Dysfunction, Left / blood
  • Ventricular Function, Left / drug effects*

Substances

  • Cytokines
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Inflammation Mediators
  • Pyrroles
  • Interleukin-10
  • Atorvastatin