FR167653, a cytokine-suppressive agent, reduces myocardial ischemia-reperfusion injury in rats.
FR167653 inhibits the production of inflammatory cytokines such as interleukin-1beta (IL-1beta) 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 occlusion-reperfusion and the time course of expression of these cytokines in myocardial tissue in rats. Myocardial infarction was induced by coronary ligation for 20 minutes followed by 2 hours of reperfusion. Although hemodynamic parameters did not differ significantly during coronary occlusion-reperfusion, the size of the infarct was significantly reduced by intravenous administration of FR167653 before occlusion (p < 0.01). mRNA levels of IL-1beta and TNF-alpha assessed by the reverse-transcriptase polymerase chain reaction method were significantly increased during coronary occlusion-reperfusion in the ischemic myocardium. Treatment with FR167653, however, significantly reduced the increased expression of these cytokines. These results indicate that the expression of inflammatory cytokines increases in the ischemic-reperfused myocardium and that the inhibition of the increased expression of cytokines by FR167653 effectively reduces myocardial ischemia-reperfusion injury.
Hoshida
S
S
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan. hoshidas@orh.go.jp
Yamashita
N
N
Otsu
K
K
Hori
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia; D016133:Polymerase Chain Reaction; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; C104334:FR 167653; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines