Tumour Necrosis Factor α Augments the Release of an Endothelium-Dependent Vasoconstrictor from Human Polymorphonuclear Leukocytes

Abstract

Summary: We have studied the effect of cytokine priming by recombinant human tumour necrosis factor α (rhTNFα) on the release of vasoactive mediators from human polymorphonuclear leukocytes (PMNs). Supernatants of human PMNs( 100 µl,5 x 107 ml, from 12 donors) relaxed precontracted rabbit aortic rings. The relaxations were preceded by a transient contraction in four experiments. In contrast, supematants of PMNs incubated with rhTNFα (0.3 n M, 30 min, 37°C) elicited variable vascular responses that consisted of either a sustained contraction (n = 4), a transient contraction followed by a sustained relaxation (n = 2), or a sustained relaxation only (n = 6). The vascular tone produced by the rhTNFα-treated PMN supernatant was significantly greater over 30 min than that produced by the control supernatant (p < 0.01). Endothelium removal prevented the PMN-induced contractions and significantly decreased the vascular tone produced by all rhTNFα-treated PMN supematants (p < 0.05). The PMN supematants had no vasoactive effect on aortic rings at resting tension. Molecular size analysis indicated that the PMN-derived contractile mediator is > 30,000 Da. These results suggest that human PMNs, primed by rhTNFα, release a stable endotheliumdependent vasoconstrictor that opposes the action of a stable, spontaneously released direct vasodilator