Methods

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-a, 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-a and NO and serves to protect the ischemic and reperfused myocardium through the suppression of neutrophil recruitment. (Circulation. 2000;101:1019-1026.) Key Words: reperfusion n interleukins n nitric oxide n cell adhesion molecules The prominent anti-inflammatory cytokine interleukin-10(IL-10) is released into the plasma of patients with myocardial ischemia/reperfusion.1–4 The production of IL-10 in many forms of shock and inflammation serves to limit the burst of proinflammatory mediators.5–9 With the use of IL-10–deficient mice, here we defined the role of endoge-nous IL-10 in the modulation of myocardial ischemia/reper-fusion injury