FR167653, a cytokine-suppressive agent, reduces myocardial ischemia-reperfusion injury in rats

FR167653 inhibits the production of inflammatory cytokines such as interleu kin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) in human monocytes In a dose-dependent manner. We examined the effects of FR167653 on the propagation of myocardial infarction resulting from coronary occlusi on-reperfusion and the time course of expression of these cytokines in myoc ardial tissue in rats. Myocardial infarction was induced by coronary ligati on for 20 minutes followed by 2 hours of reperfusion. Although hemodynamic parameters did not differ significantly during coronary occlusion-reperfusi on, the size of the infarct was significantly reduced by intravenous admini stration of FR167653 before occlusion (p < 0.01). mRNA levels of IL-1<beta> and TNF-alpha assessed by the reverse-transcriptase polymerase chain react ion method were significantly increased during coronary occlusion-reperfusi on in the ischemic myocardium. Treatment with FR167653, however, significan tly reduced the increased expression of these cytokines. These results indi cate that the expression of inflammatory cytokines increases in the ischemi c-reperfused myocardium and that the inhibition of the increased expression of cytokines by FR167653 effectively reduces myocardial ischemia-reperfusi on injury.