IL-1β primes IL-8-activated human neutrophils for elastase release, phospholipase D activity, and calcium flux

Interleukin-8 (IL-8), the prototype of the man- ner (50-1000 ngJmL) in cytochalasin B-treated hu- man polymorphonuclear leukocytes (PMNs). This response was potentiated about twofold if PMNs were preexposed to interleukin- 1 � (IL- 1 �) at concentra- tions that were by themselves inactive. The effect of IL- 1 1�was clearly observed after 5 mm and was maximal after a 30-nun preincubation of the cells. The effect was present over the whole active concen- tration range of IL-8 and was completely blocked by the presence of IL- 1 receptor antagonist. Priming of elastase release by IL- 1 � was not associated with a change in receptor number or affinity for IL-8. On the contrary, it was correlated with priming of phos- pholipase D activity and calcium flux activated by IL-8. Preincubation of the cells with ethanol and/or La3 + inhibited IL-8-induced degranulation, suggest- ing that activation of phospholipase D and increase of (Ca2 + Ji were important for this response. In contrast, ethanol and La3 + did not decrease the priming effect of IL-1�. IL-8 and IL-1� have been shown to be released by the same cell types and may be concomitantly present at sites of inflammation, giving rise to an amplification of the inflammatory response. J. Leukoc. Binl. 59: 427-434; 1996.