Plasma tumor necrosis factor-alpha during long-term endotoxemia in awake sheep

We used a continuous 12-h infusion of Escherichia coli endotoxin (10 ng · min^-1 · kg^-1) in 10 awake sheep equipped with a lung lymph fistula and vascular catheters to determine the time course of increased plasma tumor necrosis factor-alpha (TNF-α) during the infusion and a 12-h postinfusion period. Lung lymph flow increased progressively during the infusion to a peak value averaging 8.6 ± 2.0 times the baseline flow of 6.3 ± 1.3 g/h. During the postinfusion period, lung lymph flow remained elevated at three to four times baseline. The lymph-to-plasma protein concentration ratio was unchanged from baseline over 24 h, indicating a dramatic increase in net protein flux across pulmonary microvessels. The TNF-α concentration peaked early in the infusion and then declined, despite the continuing presence of endotoxin. Plasma TNF-α concentration increased 10-fold (0.33 ± 0.05 ng/ml at baseline to 3.89 ± 0.78 ng/ml peak) 2 h into the endotoxin infusion. At the end of the endotoxin infusion, plasma TNF-α had decreased to 1.16 ± 0.19 ng/ml. The circulating TNF-α concentration did not correlate with pathophysiology or outcome in these sheep.