Role of cytokines in myocardial ischemia and reperfusion

Mediators of myocardial in ammation, predomi- nantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the in ammation may result in deleterious complications for myo- cardial infarction. The proin ammatory cyto- kines may mediate myocardial dysfunction associated with myocardial infarction, severe con- gestive heart failure, and sepsis. A growing body of literature suggests that in ammatory mediators could play a crucial role in ischemia ±reperfusion injury. Furthermore, ischemia ±reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue inŽ ltration by in ammatory cells. These in ammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypox ia causes a series of well documented changes in cardiomyocytes that in- cludes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypox ic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia ± reperfusion injury. Ischemia followed by reperfu- sion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-a (TNF-a), transforming growth factor-b1 (TGF-b1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multi- potent cytokines (e.g. TNF-a) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have in- cluded a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

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