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

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• 作者：Mariuxi C. Manukyan MD^a ; ^* ; Collin H. Alvernaz^a ; ^* ; Jeffrey A. Poynter MD^a ; Yue Wang PhD^a ; Benjamin D. Brewster MD^a ; Brent R. Weil MD^a ; Aaron M. Abarbanell MD^a ; Jeremy L. Herrmann MD^a ; Brandon J. Crowe^a ; Andrew C. Keck^a ; Daniel R. Meldrum MD^a ; ^b ; ^c ; ^d ; ^{dmeldrum@iupui.edu"" rel=""nofollow}
• 刊名：Surgery
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：150
• 期：2
• 页码：231-239
• 全文大小：563 K

文摘

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.