Recombinant human tumour necrosis factor (rTNF)2 enhances leukotriene biosynthesis in neutrophils and eosinophils stimulated with the Ca2+ ionophore A23187.

Recombinant human tumour necrosis factor alpha (rTNF) did not cause the release of leukotrienes (LT) by human neutrophils and eosinophils. It did, however, prepare neutrophils and eosinophils for enhanced production of LT after activation with the calcium ionophore A23187. The effect was observed with 10(2) to 10(4) units/ml of rTNF which enhanced LTB4 production by ionophore-stimulated neutrophils, by 40 to 400%, while 10(3) to 10(4) units/ml of rTNF increased LTC4 production by ionophore-stimulated eosinophils by 30 to 120%. The enhancement was observed when granulocytes were incubated for 5 to 10 min with rTNF before stimulation with the ionophore. Increased leukotriene production was attributed to the induction of fatty acid hydrolase and/or 5-lipoxygenase activities on the basis of the increment in the total counts released after 3H-arachidonic acid labelling of neutrophils pretreated with rTNF as compared to control medium.