Serum levels of tumor necrosis factor determine the fatal or non-fatal course of endotoxic shock

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.

Neuroendocrine and Immune Responses to Acute Endotoxemia in Suckling and Weaned Piglets

“…Our study confirms that pigs respond to LPS with a marked increase in the secretion of TNF-· [13,15,51], but we failed to find a difference in circulating TNF-· concentrations between suckling and weaned piglets 1 h after LPS injection. Recently, a positive correlation between high plasma TNF-· levels and lethality caused by endotoxin shock has been reported [52], whereas a low dose of 0.5 Ìg LPS induced sickness behaviour in pigs but failed to increase plasma concentrations of TNF-· [13,14]. The dose of LPS used in our study caused similar increases in TNF-· concentrations in suckling and weaned piglets but revealed a higher intensity of sickness behaviour in weaned piglets.…”

Heat stress induces a biphasic thermoregulatory response in mice

“…Thus the presence of a feverlike state post-heat stress in our model was a novel observation that was observed via our use of biotelemetry. Evidence for the post-heat stress T c elevations as a feverlike state is as follows: 1) severe heat stress induces endotoxemia (4,9,12), 2) circulating pyrogenic cytokines increase during endotoxemia/sepsis (7,25) and heat stress (3,5), 3) the biphasic T c profiles during mouse heat stress recovery (Fig. 2) were similar to those of sepsis and fever induced by endotoxemia or cecal ligation and puncture in mice (17,22), and 4) similar to LPS-induced fever responses (19), the feverlike phase post-heat stress was noted only during the day.…”

Evaluation of the anti‐endotoxic effects of polymyxin‐E (colistin) in dogs with naturally occurred endotoxic shock

“…Several studies have shown a positive correlation between TNF‐ α levels, severity of shock and fatality (Kenison et al. , 1991; Mozes et al. , 1991; Coyne & Fenwick, 1993; Miyamoto et al.…”