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

The effects of both recombinant rat tumor necrosis factor-alpha (TNF-alpha) and an anti-TNF-alpha antibody were studied in isolated buffer-perfused ra t lungs subjected to either 45 min of nonventilated [ischemia-reperfusion ( I/R)] or air-ventilated ((V) over dot/R) ischemia followed by 90 min of rep erfusion and ventilation. In the I/R group, the vascular permeability, as m easured 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 the (V) over dot/R group incr eased five- and tenfold above baseline values, respectively (P < 0.001). TN F-alpha measured in the perfusates of both ischemic models significantly in creased after 30 min of reperfusion. Recombinant rat TNF-alpha (50,000 U), placed into perfusate after baseline measurements, produced no measurable c hange in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the pr esence of TNF-alpha. An anti-TNF-alpha antibody (10 mg/rat) injected intrap eritoneally into rats 2 h before the lung was isolated prevented the microv ascular damage in lungs exposed to both I/R and (V) over dot/R (P < 0.001). These results indicate that TNF-alpha is an essential component at the cas cade of events that cause lung endothelial injury in short-term I/R and (V) over dot/R models of lung ischemia.