Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway

Mariuxi C. Manukyan, Collin H. Alvernaz, Jeffrey A. Poynter, Yue Wang, Benjamin D. Brewster, Brent R. Weil, Aaron M. Abarbanell, Jeremy L. Herrmann, Brandon J. Crowe, Andrew C. Keck, Daniel R. Meldrum

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background: Cardiac surgery induces the release of inflammatory mediators that can prolong cardiac dysfunction after operative intervention. Interleukin-10 (IL-10), a potent inhibitor of myocardial inflammation, is a known factor in myocardial protection after ischemia/reperfusion (I/R) injury. We hypothesized that IL-10 activity during initial reperfusion is mediated through the signal transducer and activator of transcription 3 (STAT3) pathway. Methods: Adult rat hearts were isolated and perfused via Langendorff protocol and subjected to global I/R. After determining the effective IL-10 dose, hearts were administered vehicle, IL-10, or IL-10 + Stattic (specific STAT3 inhibitor) 1 min prior to ischemia. After reperfusion, hearts were sectioned and assessed for levels of myocardial inflammatory cytokines and protein. Results: The IL-10 minimum effective dose was 1 μg. IL-10-treated hearts had improved markedly myocardial function after global I/R compared to both vehicle and IL-10 + Stattic groups. In addition, IL-10 treatment was associated with a significant decrease in myocardial interleukin-1β (IL-1β) and interleukin-6 (IL-6) and increase in myocardial IL-10. Myocardial STAT3 was elevated markedly in IL-10 treated hearts. Conclusion: IL-10 improves myocardial function after acute global I/R and suppresses inflammation through the STAT3 pathway. The administration of anti-inflammatory agents may have potential therapeutic applications in cardiac surgery.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalSurgery
Volume150
Issue number2
DOIs
StatePublished - Aug 1 2011

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ASJC Scopus subject areas

  • Surgery

Cite this

Manukyan, M. C., Alvernaz, C. H., Poynter, J. A., Wang, Y., Brewster, B. D., Weil, B. R., Abarbanell, A. M., Herrmann, J. L., Crowe, B. J., Keck, A. C., & Meldrum, D. R. (2011). Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway. Surgery, 150(2), 231-239. https://doi.org/10.1016/j.surg.2011.05.017