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

Background-Previous work from our laboratory demonstrated that interleukin (IL)-6 plays a potentially critical role in postreperfusion myocardial inju ry and is the major cytokine responsible fur induction of intracellular adh esion molecule (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICA M-1 induction is necessary for neutrophil-associated myocyte injury. We hav e 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 analysi s and in situ hybridization to demonstrate IL-6 gene expression in cardiac myocytes. Isolated ventricular myocytes were stimulated with tumor necrosis factor-alpha, IL-1 beta, lipopolysaccharide, preischemic lymph, and postis chemic lymph. Unstimulated myocytes showed no significant IL-6 mRNA express ion, Myocytes stimulated with preischemic lymph showed minimal or no IL-6 m RNA expression, whereas myocytes stimulated with tumor necrosis factor-alph a, IL-1 beta, lipopolysaccharide, or postischemic lymph showed a strong IL- 6 mRNA induction. Northern blot with ICAM-1 probe revealed ICAM-1 expressio n under every condition that demonstrated IL-6 induction. We then investiga ted the expression of IL-6 mRNA in our canine model of ischemia and reperfu sion. Cardiac myocytes in the viable border zone of a myocardial infarction exhibited reperfusion-dependent expression of IL-6 mRNA within 1 hour afte r reperfusion, Mononuclear cells infiltrate the border zone and express IL- 6 mRNA. Conclusions-Isolated cardiac myocytes produce IL-6 mRNA in response to seve ral cytokines as well as postischemic cardiac lymph. In addition to its pro duction by inflammatory cells, we demonstrate that IL-6 mRNA is induced in myocytes in the viable border zone of a myocardial infarct. The potential r oles of IL-6 in cardiac myocytes in an infarct border are discussed.