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(Circulation. 1999;99:546-551.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Cardiac Myocytes Produce Interleukin-6 in Culture and in Viable Border Zone of Reperfused Infarctions
From the Section of Cardiovascular Sciences, Department of Medicine, The DeBakey Heart Center, Section of Leukocyte Biology, Department of Pediatrics, and Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
Correspondence to Mark L. Entman, MD, Department of Medicine, Section of Cardiovascular Sciences, Baylor College of Medicine, One Baylor Plaza, M/S F-602, Houston, TX 77030-3498. E-mail mentman{at}bcm.tmc.edu
Background—Previous work from our laboratory demonstrated that interleukin (IL)-6 plays a potentially critical role in postreperfusion myocardial injury and is the major cytokine responsible for induction of intracellular adhesion molecule (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICAM-1 induction is necessary for neutrophil-associated myocyte injury. We have previously demonstrated the induction of IL-6 in the ischemic myocardium, and the current study addresses the cells of origin of IL-6.
Methods and Results—In the present study, we combined
Northern blot analysis and in situ hybridization to demonstrate
IL-6 gene expression in cardiac myocytes. Isolated
ventricular myocytes were stimulated with tumor necrosis
factor-
, IL-1ß, lipopolysaccharide,
preischemic lymph, and postischemic lymph.
Unstimulated myocytes showed no significant IL-6 mRNA expression.
Myocytes stimulated with preischemic lymph showed minimal
or no IL-6 mRNA expression, whereas myocytes stimulated with tumor
necrosis factor-, IL-1ß, lipopolysaccharide, or
postischemic lymph showed a strong IL-6 mRNA induction.
Northern blot with ICAM-1 probe revealed ICAM-1 expression under every
condition that demonstrated IL-6 induction. We then investigated the
expression of IL-6 mRNA in our canine model of ischemia and
reperfusion. Cardiac myocytes in the viable border zone of a myocardial
infarction exhibited reperfusion-dependent expression of IL-6 mRNA
within 1 hour after reperfusion. Mononuclear cells infiltrate the
border zone and express IL-6 mRNA.
Conclusions—Isolated cardiac myocytes produce IL-6 mRNA in response to several cytokines as well as postischemic cardiac lymph. In addition to its production by inflammatory cells, we demonstrate that IL-6 mRNA is induced in myocytes in the viable border zone of a myocardial infarct. The potential roles of IL-6 in cardiac myocytes in an infarct border are discussed.
Key Words: interleukins • myocardial infarction • reperfusion • myocytes
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