TY - JOUR
T1 - Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway
AU - Manukyan, Mariuxi C.
AU - Alvernaz, Collin H.
AU - Poynter, Jeffrey A.
AU - Wang, Yue
AU - Brewster, Benjamin D.
AU - Weil, Brent R.
AU - Abarbanell, Aaron M.
AU - Herrmann, Jeremy L.
AU - Crowe, Brandon J.
AU - Keck, Andrew C.
AU - Meldrum, Daniel R.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.surg.2011.05.017
DO - 10.1016/j.surg.2011.05.017
M3 - Article
C2 - 21719057
AN - SCOPUS:79960916464
SN - 0039-6060
VL - 150
SP - 231
EP - 239
JO - Surgery
JF - Surgery
IS - 2
ER -