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J Cardiovasc Pharmacol. 2017 Mar;69(3):156-160. doi: 10.1097/FJC.0000000000000452.

Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha.

Author information

1
*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.

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).

CONCLUSION:

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.

PMID:
28267688
DOI:
10.1097/FJC.0000000000000452
[Indexed for MEDLINE]

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