Leukotriene and prostaglandin production after infusion of tumour necrosis factor in man

Tumor necrosis factor-alpha is believed to be an important mediator of endotoxaemia and septic shock, the effects of which are thought to be mediated through the generation of cysteinyl-leukotrienes, thromboxane A₂ and other prostanoids. We have investigated the production of these eicosanoids and also that of prostacyclin in vivo after infusion of tumor necrosis factor-alpha into 4 subjects with a chronic hepatitis B virus infection. This resulted in plasma TNF levels considerably greater than those observed in septic shock. Urinary excretion rate of leukotriene E₄ increased by 2 to 3-fold in all subjects by 8 h following TNF infusion. Urinary excretion of thromboxane B₂ and 6-oxo-prostaglandin F(1α), however, increased in the first 4 h in 3/4 subjects by 2 to 40-fold and returned towards baseline by 8 h. Excretion of the hepatic metabolite, 2,3-dinor 6-oxo-prostaglandin F(1α), increased in all subjects (2 to 4-fold at 4 h). We conclude that there is increased production of cysteinyl leukotrienes, thromboxane A₂ and prostacyclin after infusion of tumour necrosis factor into man.