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J Appl Physiol 73: 1831-1837, 1992;
8750-7587/92 $5.00
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Journal of Applied Physiology, Vol 73, Issue 5 1831-1837, Copyright © 1992 by American Physiological Society

ARTICLES

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

P. J. Sloane, T. H. Elsasser, J. A. Spath Jr, K. H. Albertine and M. H. Gee
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

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-alpha) 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-alpha concentration peaked early in the infusion and then declined, despite the continuing presence of endotoxin. Plasma TNF-alpha 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-alpha had decreased to 1.16 +/- 0.19 ng/ml. The circulating TNF-alpha concentration did not correlate with pathophysiology or outcome in these sheep.


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