LEUKEMIA INHIBITORY FACTOR AND TUMOR-NECROSIS-FACTOR INDUCE MANGANESESUPEROXIDE-DISMUTASE AND PROTECT RABBIT HEARTS FROM REPERFUSION INJURY

Leukemia inhibitory factor (LIF) and tumor necrosis factor (TNF) have been shown to protect animals from radiation, hyperoxia, and endotoxic shock. TNF is also known to induce the expression of manganese supero xide dismutase (MnSOD) in vitro and in vivo. We therefore examined the effects of these cytokines on reperfusion injury in the isolated rabb it heart model. Rabbits were injected intravenously with 10 mu g of ei ther human TNF-alpha or lymphotoxin (TNF-beta), or murine TNF-alpha or murine LIF dissolved in saline, Control animals were injected with an equal volume of saline, After 24 h, hearts were isolated and perfused , Following an equilibration period, the hearts were subjected to 1 h ischemia and 1 h of reperfusion, All treated groups showed significant increases in percent recovery of developed tension (% preischemic) wh en compared to saline-treated control hearts. In addition there were s ignificant decreases in lactate dehydrogenase release (LDH), accumulat ion of thiobarbituric acid reactive substances (TEARS), and accumulati on of carbonyl proteins, These results correlate with increases in myo cardial MnSOD activity, Thus, the protection from myocardial reperfusi on injury seen in the pretreated group may be due to a mechanism that involves the induction of MnSOD.