Antibody Against interleukin-6 Receptor Attenuates Left Ventricular Remodelling After Myocardial Infarction in Mice

Cardiovasc Res. 2010 Aug 1;87(3):424-30. doi: 10.1093/cvr/cvq078. Epub 2010 Mar 7.

Abstract

Aims: The plasma level of interleukin-6 (IL-6) has been reported to be associated with left ventricular (LV) remodelling after myocardial infarction (MI). The present study was designed to examine whether anti-IL-6 receptor antibody (MR16-1) prevents the development of LV remodelling after MI.

Methods and results: Balb/c male mice were subjected to MI by ligating the left anterior descending coronary artery. The mice were then treated with an intraperitoneal injection of MR16-1 (500 microg/body) or control IgG. MR16-1 decreased the myocardial myeloperoxidase activity and monocyte chemoattractant protein-1 concentration in the infarct region, concomitant with decreases in neutrophil and macrophage infiltration 3 days after ligation, while infarct size was comparable between the control IgG- and MR16-1-treated mice. At 7 days after ligation, MR16-1 significantly suppressed matrix metalloproteinase-2 activity in the infarct region. Furthermore, the MR16-1-treated mice demonstrated a reduction in LV dilatation and an improvement in LV contractile function compared with the control IgG-treated mice at 7 and 28 days after surgery, leading to an improvement in survival rate (80.6 vs. 59.5%, P < 0.05) at 28 days after surgery. The beneficial effects of MR16-1 were accompanied by histological suppression of cardiomyocyte hypertrophy and interstitial fibrosis in the non-infarct region.

Conclusion: Administration of MR16-1 after MI suppressed myocardial inflammation, resulting in the amelioration of LV remodelling. Neutralization of the IL-6 receptor is a potentially useful strategy for protecting hearts from LV remodelling after MI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / pharmacology*
  • Apoptosis
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Injections, Intraperitoneal
  • Interleukin-6 / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / immunology
  • Myocardial Infarction / physiopathology
  • Myocardium / immunology*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Neutrophil Infiltration / drug effects
  • Peroxidase / metabolism
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / immunology
  • Time Factors
  • Ultrasonography
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling / drug effects*

Substances

  • Antibodies, Neutralizing
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Interleukin-6
  • Receptors, Interleukin-6
  • Peroxidase
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse