Tumor necrosis factor-α in ischemia and reperfusion injury in rat lungs

Abstract

The effects of both recombinant rat tumor necrosis factor-α (TNF-α) and an anti-TNF-α antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V˙/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascular permeability, as measured by the filtration coefficient ( K fc), increased three- and fivefold above baseline after 30 and 90 min of reperfusion, respectively ( P < 0.001). Over the same time intervals, the K fc for theV˙/R group increased five- and tenfold above baseline values, respectively ( P < 0.001). TNF-α measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-α (50,000 U), placed into perfusate after baseline measurements, produced no measurable change in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the presence of TNF-α. An anti-TNF-α antibody (10 mg/rat) injected intraperitoneally into rats 2 h before the lung was isolated prevented the microvascular damage in lungs exposed to both I/R and V˙/R ( P < 0.001). These results indicate that TNF-α is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R andV˙/R models of lung ischemia.