title: Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha.
abstract: BACKGROUND
  Interleukin-1α (IL-1α) released by dying cells is an alarmin that activates the innate immunity. We hypothesized that after myocardial ischemia-reperfusion (I/R) injury, IL-1α amplifies the myocardial damage by activating the inflammasome and caspase-1.
  
  
  METHODS
  Adult male CD1 mice were used. The left anterior descending coronary artery was ligated for 30 minutes, after 24 hours of reperfusion. An IL-1α blocking antibody (15 μg/kg intraperitoneally) or matching vehicle was given after reperfusion. A subgroup of mice underwent sham surgery. We assessed the effects of IL-1α blockade on caspase-1 activity, infarct size, cardiac troponin I serum levels, and left ventricular fractional shortening, 24 hours after I/R.
  
  
  RESULTS
  I/R led to inflammasome formation, and IL-1α blockade significantly reduced inflammasome formation, reflected by a >50% reduction in caspase-1 activity versus vehicle (P = 0.03). IL-1α blockade also reduced the infarct size (-52% infarct expressed as percentage of area at risk, and -79% for cardiac troponin I serum levels, P < 0.001 vs. vehicle) and preserved the left ventricular fractional shortening (31 ± 3% vs. 25 ± 2%, P < 0.001 vs. vehicle).
  
  
  CONCLUSIONS
  IL-1α blockade after I/R reduces the inflammasome activation, decreases the infarct size, and preserves the left ventricular function. IL-1α blockade may therefore represent a novel therapeutic strategy to reduce I/R injury.
authors.affiliation: *VCU Pauley Heart Center, Virginia Comonwealth University, Richmond, VA;†VCU Johnson Research Center, Virginia Comonwealth University, Richmond, VA;‡Department of Biomedical, Biotechnological, and Translational Sciences, University of Parma, Parma, Italy;§Department of Pharmacotherapy and Outcome Sciences, School of Pharmacy, Virginia Comonwealth University, Richmond, VA;¶Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; and‖Department of Surgery, Virginia Commonwealth University, Richmond, VA.
authors.forename: Adolfo G
authors.initials: AG
authors.lastname: Mauro
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mezzaroma
authors.forename: Juan
authors.initials: J
authors.lastname: Torrado
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kundur
authors.forename: Priyashma
authors.initials: P
authors.lastname: Joshi
authors.forename: Kelsey
authors.initials: K
authors.lastname: Stroud
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.forename: Costanza A
authors.initials: CA
authors.lastname: Lagrasta
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
mesh_terms: D000818:Animals; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D011897:Random Allocation
chemical_list: D007155:Immunologic Factors; D053582:Interleukin-1alpha