Leukemia inhibitory factor and tumor necrosis factor induce manganese superoxide 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 superoxide dismutase (MnSOD) in vitro and in vivo. We therefore examined the effects of these cytokines on reperfusion injury in the isolated rabbit heart model. Rabbits were injected intravenously with 10 micrograms of either 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) when compared to saline-treated control hearts. In addition there were significant decreases in lactate dehydrogenase release (LDH), accumulation of thiobarbituric acid reactive substances (TBARS), and accumulation of carbonyl proteins. These results correlate with increases in myocardial MnSOD activity. Thus, the protection from myocardial reperfusion injury seen in the pretreated group may be due to a mechanism that involves the induction of MnSOD.
Nelson
S K
SK
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262, USA.
Wong
G H
GH
McCord
J M
JM
D000704:Analysis of Variance; D000818:Animals; D004790:Enzyme Induction; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6; D007770:L-Lactate Dehydrogenase; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D051379:Mice; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*; D011292:Premedication; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase