Endotoxin-induced cytokine gene expression in vivo. I. Expression of tumor necrosis factor mRNA in visceral organs under physiologic conditions and during endotoxemia.

Tumor necrosis factor (TNF) mRNA was detected by Northern blotting in whole-organ homogenates of the spleen, liver, kidney, lung, and small bowel in naive and saline-injected control rats, supporting the hypothesis that TNF mRNA is present in vivo in a preformed intracellular pool. TNF mRNA in endotoxin-treated rats as quantitated by densitometry of the ratio of TNF mRNA to actin mRNA in Northern blots was present in increased quantity in the liver, kidney, and lung (1.6-2.9 times over time zero levels) at 15 minutes and increased quantity in the spleen, liver, and kidney (1.3-1.9 times over time zero levels) at 30 minutes. The kinetics of endotoxin-induced TNF gene expression are consistent with the relatively transient peak of serum TNF protein levels reported by previous investigators to occur approximately 1 hour after injection of endotoxin. Because TNF mRNA appeared ubiquitous in the organs of control rats examined and because the endotoxin-induced increase in TNF mRNA was relatively small, endotoxin may induce the expression of the TNF protein in serum not only by increasing TNF mRNA levels but perhaps more importantly by a posttranscriptional mechanism. The presence of a preformed pool of TNF mRNA may teleologically be viewed as a mechanism to increase the rapidity of the host's response to sepsis.