title: Antibody against interleukin-6 receptor attenuates left ventricular remodelling after myocardial infarction in mice.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pathological Science, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, 5 Misasagi Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan. kobara@mb.kyoto-phu.ac.jp
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobara
authors.forename: Kazuki
authors.initials: K
authors.lastname: Noda
authors.forename: Miho
authors.initials: M
authors.lastname: Kitamura
authors.forename: Akiharu
authors.initials: A
authors.lastname: Okamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Hiroe
authors.initials: H
authors.lastname: Toba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakata
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D057134:Antibodies, Neutralizing; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D009195:Peroxidase; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse