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

• Published in: Circulation (New York, N.Y.) N.Y.), 1999-02, Vol.99 (4), p.546-551
• Main Authors: GWECHENBERGER, M, MENDOZA, L. H, YOUKER, K. A, FRANGOGIANNIS, N. G, SMITH, C. W, MICHAEL, L. H, ENTMAN, M. L
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Northern; Cardiology. Vascular system; Cells, Cultured; Coronary Circulation; Coronary heart disease; Dogs; Female; Gene Expression Regulation; Heart; Heart Ventricles - cytology; Heart Ventricles - metabolism; Heart Ventricles - physiopathology; In Situ Hybridization; Intercellular Adhesion Molecule-1 - biosynthesis; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Male; Medical sciences; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; RNA, Messenger - analysis
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.99.4.546

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. 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-alpha, IL-1beta, 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-alpha, IL-1beta, 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. 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.