title: Recombinant human interleukin-1 receptor antagonist provides cardioprotection during myocardial ischemia reperfusion in the mouse.
abstract: OBJECTIVE
  Acute myocardial infarction (AMI) drives an intense inflammatory response that contributes to infarct healing and cardiac remodeling. Recently, different studies have identified a role of interleukin-1 (IL-1) in the development of adverse cardiac remodeling. However, in animal models of AMI IL-1 has been shown to be cardioprotective in preconditioning, raising the question of clinical safety of therapeutic IL-1 blockade for autoinflammatory diseases or for the prevention or the treatment of AMI. In this study we proposed to evaluate the effects of pretreatment with recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on ischemia reperfusion (I/R) injury to the heart.
  
  
  METHODS
  RhIL-1Ra was given 4 h or 30 min before the surgical induction of I/R. Left ventricular ejection fraction(LVEF) and infarct size were assessed to determine the effects of the drug pretreatment compared to vehicle treated mice.
  
  
  RESULTS
  RhIL-1Ra, given 4 h or 30 min before the onset of the ischemia, showed marked cardioprotection though preservation of the LVEF (no change vs sham operated mice) and the reduction of the infarct size (-40 % vs vehicle-treated mice). No differences were observed between the two groups of rhIL-1Ra treatment.
  
  
  CONCLUSIONS
  IL-1 blockade therapies using rhIL-1Ra prior the onset of AMI protects the myocardium and preserves cardiac function.
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, 1200 E. Broad St. 10th floor, Richmond, VA 23298, USA. stoldo2@vcu.edu
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Schatz
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mezzaroma
authors.forename: Raveen
authors.initials: R
authors.lastname: Chawla
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Stallard
authors.forename: William C
authors.initials: WC
authors.lastname: Stallard
authors.forename: Arehzo
authors.initials: A
authors.lastname: Jahangiri
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011994:Recombinant Proteins