INTERLEUKIN-6 (IL-6) AS A MEDIATOR OF STUNNED MYOCARDIUM

Proinflammatory cytokines are a class of secretory polypeptides that are synthesized and released locally by macrophages, leukocytes and endothelial cells in response to injury.1-4 Reperfusion of ischemic myocardium is associated with infiltration by leukocytes and macrophages that may be responsible for transient depression in myocardial contractility ("stunned myocardium"). 1,2 We have recently demonstrated that certain cytokines (IL-2, IL-6, and TNFα) have direct, reversible negative inotropic effects in isolated hamster papillary muscle preparations.5 The observed inotropic effects of these cytokines raised the possibility that they contribute to myocardial stunning. A direct effect of cytokines on human myocardium in concentrations achievable clinically would be necessary to further support this hypothesis. The frequency of myocardial stunning after cardiopulmonary bypass provided an ideal opportunity to assay the levels as well as the inotropic effects of these cytokines in human hearts. Written, informed consent was obtained from patients undergoing elective aortocoronary bypass grafting in accordance with the guidelines of the University of Pittsburgh Institutional Review Board for Biomedical Research. The elaboration of cytokines by pulmonary macrophages in response to injury suggested that pulmonary venous blood might be a rich source of inflammatory cytokines after cardiopulmonary bypass.6 Plasma levels of TNFα and IL-6 in pulmonary venous effluents were measured from 7 patients immediately before and after uncomplicated coronary artery bypass grafting. © 1993.