Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions

Marianne Gwechenberger, Leonardo H. Mendoza, Keith A. Youker, Nikolaos G. Frangogiannis, C. Wayne Smith, Lloyd H. Michael, Mark L. Entman

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247 Scopus citations

Abstract

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-2a, IL-1β, 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- α, IL-1b, 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.

Original languageEnglish (US)
Pages (from-to)546-551
Number of pages6
JournalCirculation
Volume99
Issue number4
DOIs
StatePublished - Feb 2 1999
Externally publishedYes

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Keywords

  • Interleukins
  • Myocardial infarction
  • Myocytes
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Gwechenberger, M., Mendoza, L. H., Youker, K. A., Frangogiannis, N. G., Wayne Smith, C., Michael, L. H., & Entman, M. L. (1999). Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation, 99(4), 546-551. https://doi.org/10.1161/01.CIR.99.4.546