title: Interleukin-1β blockade improves left ventricular systolic/diastolic function and restores contractility reserve in severe ischemic cardiomyopathy in the mouse.
abstract: BACKGROUND
  Interleukin-1β (IL-1β) modulates the inflammatory response during acute myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated whether blockade of IL-1β after the onset of the cardiac dysfunction prevented left ventricular (LV) adverse remodeling in a mouse model of anterior nonreperfused AMI.
  
  
  METHODS
  Infarct size and LV systolic function were assessed by echocardiography 7 days after coronary artery ligation. Mice with large infarct size and LV ejection fraction (LVEF) <40% were randomly assigned to treatment with a monoclonal antibody directed toward IL-1β antibody (10 mg/kg IL-1β-AB) or with a cyclosporine directed antibody (10 mg/kg control-AB). Echocardiogram was repeated after 10 weeks, followed by assessment of contractile reserve using isoproterenol challenge and LV catheterization.
  
  
  RESULTS
  After 10 weeks, control-AB-treated mice showed significantly increased LV end-diastolic diameter (+15%, P < 0.001) and decreased LVEF (-18%, P = 0.050). IL-1β-AB had no significant effect on LV end-diastolic diameter (+10%, P = 0.25 vs. control-AB) but significantly prevented LVEF reduction (+7%, P = 0.031 vs. control-AB), enlargement of the right ventricle (P = 0.024), impairment in myocardial performance index (P = 0.028) and contractile reserve (P = 0.008), and increased LV end-diastolic pressure (P = 0.030).
  
  
  CONCLUSIONS
  IL-1β blockade using a monoclonal antibody in mice with severe LV dysfunction after AMI prevents further deterioration in LV systolic and diastolic function and restores contractile reserve.
authors.affiliation: *Virginia Commonwealth University Pauley Heart Center, Virginia Commonwealth University, Richmond, VA; †Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA; and ‡Department of Pharmacotherapy and Outcome Studies, Virginia Commonwealth University, Richmond, VA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mezzaroma
authors.forename: Edoardo
authors.initials: E
authors.lastname: Bressi
authors.forename: Carlo
authors.initials: C
authors.lastname: Marchetti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Carbone
authors.forename: Chiara
authors.initials: C
authors.lastname: Sonnino
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004452:Echocardiography; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000276:immunology; D009203:Myocardial Infarction / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000276:immunology / Q000628:therapy*; D012720:Severity of Illness Index; D018487:Ventricular Dysfunction, Left / Q000276:immunology / Q000628:therapy; D016277:Ventricular Function, Left / Q000276:immunology; D020257:Ventricular Remodeling / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D053583:Interleukin-1beta; D007545:Isoproterenol