Anakinra in Experimental Acute Myocardial Infarction--Does Dosage or Duration of Treatment Matter?

Cardiovasc Drugs Ther. 2009 Apr;23(2):129-35. doi: 10.1007/s10557-008-6154-3. Epub 2008 Nov 13.

Abstract

Purpose: Interleukin-1 (IL-1) receptor antagonist (Ra) is a naturally occurring IL-1 blocker with a cardioprotective effect during acute myocardial infarction (AMI). Anakinra, recombinant-human IL-1Ra, has been used to prevent heart failure in a mouse model of AMI. The aim of this study was to determine the optimal therapeutic regimen for anakinra in AMI.

Methods: We performed dose-response experiments comparing anakinra 1 mg/kg with 100 mg/kg doses, and duration-response experiments comparing 1-week to 2-week treatment. Echocardiography was used to assess cardiac remodeling and systolic function. Histopathology was used to detect apoptotic cardiomyocytes.

Results: A higher dose of anakinra was not associated with additional improvement in cardiac remodeling or function. The 2-week anakinra treatment had sustained and more favorable remodeling and systolic function compared to 1-week treatment with significantly smaller left ventricular end-systolic diameter and greater fractional shortening 4 weeks after AMI.

Conclusion: Anakinra inhibits apoptosis and ameliorates cardiac remodeling up to 4 weeks after infarction. A 2-week regimen is superior to a 1-week regimen, whereas a higher dose did not provide any further benefit over standard doses.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Echocardiography
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage
  • Interleukin 1 Receptor Antagonist Protein / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardial Infarction / drug therapy*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology
  • Time Factors
  • Ventricular Remodeling / drug effects

Substances

  • Cardiotonic Agents
  • Interleukin 1 Receptor Antagonist Protein