title: Interleukin-1 trap attenuates cardiac remodeling after experimental acute myocardial infarction in mice.
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.
authors.affiliation: Pauley Heart Center, Virginia Commonwealth University, Richmond, 23298-0281, USA.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.forename: Amit
authors.initials: A
authors.lastname: Varma
authors.forename: Fadi N
authors.initials: FN
authors.lastname: Salloum
authors.forename: Anindita
authors.initials: A
authors.lastname: Das
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Seropian
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.forename: Lisa
authors.initials: L
authors.lastname: Smithson
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Hoke
authors.forename: Vinh Q
authors.initials: VQ
authors.lastname: Chau
authors.forename: Roshanak
authors.initials: R
authors.lastname: Robati
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000008:administration & dosage* / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D053583:Interleukin-1beta; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C531377:rilonacept