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-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.
Sloane
P J
PJ
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Elsasser
T H
TH
Spath
J A
JA
Albertine
K H
KH
Gee
M H
MH
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001798:Blood Proteins / Q000378:metabolism; D017536:Carotid Artery, Common / Q000502:physiology; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005260:Female; D006400:Hematocrit; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008208:Lymphatic System / Q000502:physiology; D012756:Sheep; D014160:Transducers, Pressure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001798:Blood Proteins; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha