title: Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Mariuxi C
authors: MC
authors: Manukyan
authors: Collin H
authors: CH
authors: Alvernaz
authors: Jeffrey A
authors: JA
authors: Poynter
authors: Yue
authors: Y
authors: Wang
authors: Benjamin D
authors: BD
authors: Brewster
authors: Brent R
authors: BR
authors: Weil
authors: Aaron M
authors: AM
authors: Abarbanell
authors: Jeremy L
authors: JL
authors: Herrmann
authors: Brandon J
authors: BJ
authors: Crowe
authors: Andrew C
authors: AC
authors: Keck
authors: Daniel R
authors: DR
authors: Meldrum
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000008:administration & dosage*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D050796:STAT3 Transcription Factor; D016753:Interleukin-10