Interleukin-1 trap attenuates cardiac remodeling after experimental acute myocardial infarction in mice

J Cardiovasc Pharmacol. 2010 Feb;55(2):117-22. doi: 10.1097/FJC.0b013e3181c87e53.

Abstract

Background: Interleukin-1 (IL-1) is an inflammatory cytokine that responds as an acute phase reactant during acute myocardial infarction. Conflicting data describe the role of anti-IL-1 interventions to reduce cardiac remodeling after AMI. IL-1 Trap is a modified recombinant fusion protein that binds circulating IL-1. Our study evaluated the effects of murine IL-1 Trap on cardiac remodeling after AMI resulting from permanent surgical coronary artery ligation.

Methods: Mice received treatment with intraperitoneal injection of murine IL-1 Trap (1 mg/kg [n = 5], 5 mg/kg [n = 5], or 30 mg/kg [n = 5]) or NaCl 0.9% (saline; n = 10) every 48 hours after surgery. Transthoracic echocardiography was performed at baseline and 7 days after surgery. Inhibition of IL-1 signaling was determined by measurement of IL-6 plasma levels (enzyme-linked immunosorbent assay) after IL-1b injection. Apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) was measured in murine heart samples and in a primary culture of murine cardiomyocytes.

Results: Mice treated with 5 mg/kg or 30 mg/kg IL-1 Trap had more favorable cardiac remodeling and echocardiographic assessment of infarct size at 7 days compared with saline (P < 0.05 for each comparison). Treatment with IL-1 Trap also reduced apoptosis and IL-6 levels compared with saline treatment.

Conclusions: IL-1 Trap ameliorates cardiac remodeling and reduces cardiomyocyte apoptosis after experimental acute myocardial infarction in the mouse.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / physiology
  • Cells, Cultured
  • Disease Models, Animal*
  • Interleukin-1beta / administration & dosage*
  • Interleukin-1beta / physiology
  • Interleukin-6 / antagonists & inhibitors
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / physiology
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / therapeutic use*
  • Signal Transduction / physiology
  • Ventricular Remodeling / physiology*

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Recombinant Fusion Proteins
  • rilonacept