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The relationship between gut-derived endotoxemia and tumor necrosis factor, neopterin: experimental and clinical
1p6auma Research Center, Postgraduate Medical College, 304th Hospital of People's Liberation Army, Beijing.
Objective:
To determine the relationship between gut-derived endotoxemia and tumor necrosis factor (TNF), neopterin/biopterin formation following hemorrhage, trauma and burns.
Methods:
Rats were subjected to hemorrhagic shock (30 mmHg, 90-180 min) and 40% III degrees thermal injury. Circulating endotoxin, TNF, biopterin levels and liver TNF mRNA expression were measured in animals following acute insults. Also, the subjects of this study included 35 patients with burn size greater than 30%, and 25 patients with multiple injuries (n = 18) and major surgery (n = 7).
Results:
It was found that significant portal and systemic endotoxemia took place in the control animal after hemorrhagic shock and thermal injury, but almost not in the animals that treated by measures aiming at controlling endotoxin/bacteria translocation, including polymyxin B, monoclonal antibody against core lipopolysaccharide, and selective decontamination of the digestive tract (SDD). Concomitantly, hemorrhage and thermal injury resulted in significant increases in systemic plasma TNF level together with tissue TNF mRNA expression, which were associated with the initial appearance of endotoxin in portal vein. However, anti-endotoxin treatment markedly decreased circulating TNF level as well as peak TNF mRNA expression caused by acute insults. There were also lower serum biopterin values in the SDD-treated group as compared with the control group on day 5 postburn. On the other hand, the results showed that the amounts of plasma endotoxin in patients increased during the early stages following major burns, which was significantly correlated with plasma TNF levels, particularly in patients who developed sepsis and multiple organ failure. Although the presence of early endotoxemia did not influence the alterations in serum neopterin, patients with endotoxemia had much higher neopterin values than those who showed no endotoxemia from the second week onward.
Conclusion:
These results suggest that gut-derived endotoxemia could account, at least in part, for the inflammatory mediators formation and release, which might be involved in the pathogenesis of sepsis and multiple organ dysfunction following severe hemorrhage, trauma and burns.