title: Anakinra in experimental acute myocardial infarction--does dosage or duration of treatment matter?
abstract: OBJECTIVE
  Interleukin-1 (IL-1) receptor antagonist (Ra) is a naturally occurring IL-1 blocker with a cardioprotective effect during acute myocardial infarction (AMI). Anakinra, recombinant-human IL-1Ra, has been used to prevent heart failure in a mouse model of AMI. The aim of this study was to determine the optimal therapeutic regimen for anakinra in AMI.
  
  
  METHODS
  We performed dose-response experiments comparing anakinra 1 mg/kg with 100 mg/kg doses, and duration-response experiments comparing 1-week to 2-week treatment. Echocardiography was used to assess cardiac remodeling and systolic function. Histopathology was used to detect apoptotic cardiomyocytes.
  
  
  RESULTS
  A higher dose of anakinra was not associated with additional improvement in cardiac remodeling or function. The 2-week anakinra treatment had sustained and more favorable remodeling and systolic function compared to 1-week treatment with significantly smaller left ventricular end-systolic diameter and greater fractional shortening 4 weeks after AMI.
  
  
  CONCLUSIONS
  Anakinra inhibits apoptosis and ameliorates cardiac remodeling up to 4 weeks after infarction. A 2-week regimen is superior to a 1-week regimen, whereas a higher dose did not provide any further benefit over standard doses.
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298-0281, USA.
authors.forename: Fadi N
authors.initials: FN
authors.lastname: Salloum
authors.forename: Vinh
authors.initials: V
authors.lastname: Chau
authors.forename: Amit
authors.initials: A
authors.lastname: Varma
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Hoke
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.forename: Giuseppe G L
authors.initials: GG
authors.lastname: Biondi-Zoccai
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
authors.forename: George W
authors.initials: GW
authors.lastname: Vetrovec
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D053590:Interleukin 1 Receptor Antagonist Protein