No abstract

The role of tumor necrosis factor alpha (TNFo0 in endotoxin-induced shock was investigated in pigs receiving 5/~g kg -~ of Escherichia coli endotoxin (LPS)during 60 rain of continuous infusion intothe superior mesenteric artery. I_PS concentration in aortic plasma, as determined by a chromogenic Limtdus amoebocyte lysate (LAL) test, reached a peak of approximately 1000 ng I -t during LPS infusion, and declined rapidly after discontinuation of the infusion. Serum TNF levels were determined by a bioassay using the L929 murine transformed fibroblast line. Eight of the 17 animals infused with LPS died within 30 min after beginning LPS administration, while the other 9 pigs survived beyond the experimental observation period of 3 h, although they were in a state of shock. No difference in LPS concentration was found between the surivors and the non-survivors. However, the serum TNF levels in non-survivors were significantly higher than in sur~,ivors when measured at 30 min after beginning LPS administration. In survivors, the peak increase in serum TNF levels was measured at 60 rain after the beginning of LPS injection and returned rapidly to the baseline values. Although the role of TNF inducing rapid death seems to be dominant, the hemodynamic, hematology and blood chemistry disturbances seen during shock continued in survivors long after the return of TNF to baseline levels. These findings indicate that besides TNF other mediators are also invol~ed in the LPS infusioninduced shock.