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


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-alpha, 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-alpha and NO and serves to protect the ischemic and reperfused myocardium through the suppression of neutrophil recruitment.
Yang
Z
Z
Children's Hospital Medical Center, Division of Critical Care, Cincinnati, OH, USA.
Zingarelli
B
B
Szabó
C
C
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology*; D006439:Hemodynamics; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D009569:Nitric Oxide