(Circulation. 2000;101:1019.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Crucial Role of Endogenous Interleukin-10 Production in Myocardial Ischemia/Reperfusion Injury
From the Children’s Hospital Medical Center (Z.Y., B.Z., C.S.), Division of Critical Care, Cincinnati, Ohio; and Inotek Corporation (C.S.), Beverly, Mass.
Correspondence to Csaba Szabó, MD, PhD, Inotek Corporation, Suite 419 E, 100 Cummings Center, Beverly, MA 01915. E-mail szabocsaba{at}aol.com
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-
, 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- and NO and serves to
protect the ischemic and reperfused myocardium
through the suppression of neutrophil recruitment.
Key Words: reperfusion • interleukins • nitric oxide • cell adhesion molecules
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