ROLE OF CYTOKINES IN MYOCARDIAL-ISCHEMIA AND REPERFUSION

Mediators of myocardial inflammation, predominantly cytokines, have fo r many years been implicated in the healing processes after infarction . In recent years, however, more attention has been paid to the possib ility that the inflammation may result in deleterious complications fo r myocardial infarction. The proinflammatory cytokines may mediate myo cardial dysfunction associated with myocardial infarction, severe cong estive heart failure, and sepsis. A growing body of literature suggest s that inflammatory mediators could play a crucial role in ischemia-re perfusion injury. Furthermore, ischemia-reperfusion not only results i n the local transcriptional and translational upregulation of cytokine s but also leads to tissue infiltration by inflammatory cells. These i nflammatory cells are a ready source of a variety of cytokines which c ould be lethal for the cardiomyocytes. At the cellular level it has be en shown that hypoxia causes a series of well documented changes in ca rdiomyocytes that includes loss of contractility, changes in lipid met abolism and subsequent irreversible cell membrane damage leading to ce ll death. For instance, hypoxic cardiomyocytes produce interleukin-6 ( IL-6) which could contribute to the myocardial dysfunction observed in ischemiareperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor ne crosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF -beta 1) as well as an angiogenic cytokine/ growth factor, vascular en dothelial growth factor (VEGF), in the heart. Intrestingly, these mult ipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotecti ve response in the reperfused myocardium. In this review, we have incl uded a number of cytokines that may contribute to ventricular dysfunct ion and/or to the cytoprotective and adaptive changes in the reperfuse d heart.