Crucial role of endogenous interleukin-10 production in myocardial ischemia/reperfusion injury

Zequan Yang, Basilia Zingarelli, Csaba Szabó

    Research output: Contribution to journalArticle

    226 Scopus citations

    Abstract

    Background - The anti-inflammatory cytokine interleukin-10 (IL-10) has been detected in the plasma of patients with myocardial ischemia/reperfusion. The aim of our study was to investigate the role of endogenously produced IL-10 in myocardial ischemia/reperfusion. Methods and Results - In the present study, we used wild-type and IL-10-deficient mice subjected to myocardial ischemia/reperfusion. Significant levels of IL-10 were produced in wild-type mice at 2 to 6 hours after myocardial reperfusion. The genetic deletion of IL-10 enhanced neutrophil infiltration into the reperfused tissues at 6 hours after reperfusion and increased infarct size and myocardial necrosis. Furthermore, in the absence of IL-10, an enhancement of the inflammatory response was seen, as demonstrated by increased plasma levels of tumor necrosis factor-α, nitrite/nitrate (breakdown products of NO), and increased tissue expression of intercellular adhesion molecule-1. Reperfusion for 24 hours was associated with a 75% mortality rate in IL-10-deficient mice, whereas no deaths occurred in the wild-type animals. Conclusions -The present findings provide the first direct evidence that endogenous IL-10 inhibits the production of tumor necrosis factor-α and NO and serves to protect the ischemic and reperfused myocardium through the suppression of neutrophil recruitment.

    Original languageEnglish (US)
    Pages (from-to)1019-1026
    Number of pages8
    JournalCirculation
    Volume101
    Issue number9
    DOIs
    StatePublished - Mar 7 2000

    Keywords

    • Cell adhesion molecules
    • Interleukins
    • Nitric oxide
    • Reperfusion

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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