INTERLEUKIN-1-BETA PRIMES INTERLEUKIN-8-STIMULATED CHEMOTAXIS AND ELASTASE RELEASE IN HUMAN NEUTROPHILS VIA ITS TYPE-I RECEPTOR

Interleukin-1 (IL-1) is a pleiotropic proinflammatory cytokine which b inds to human neutrophils (PMN) and can directly or indirectly activat e their functions, In this study we show that a brief exposure to IL-1 beta induces a potentiation of both PMN elastase release and chemotac tic response to interleukin-8 (IL-8), the prototype of C-X-C chemokine s. Priming by IL-1 beta was maximal at 100 ng/ml, was completely block ed in the presence of IL-1 receptor antagonist (IL-1ra) and, in the ch emotaxis assay, was best observed at suboptimal (3-6 ng/ml) or inactiv e (0.75 ng/ml) concentrations of IL-8, Priming of PMN by IL-1 beta was completely blocked by M1, a specific antibody against the type I IL-1 receptor (IL-1RI), On the other hand M22, an antibody directed agains t the IL-1 decoy type II IL-1 receptor did not affect IL-1 beta action and slightly increased the priming effect, Thus, exclusively via its type I receptor, IL-1 beta can act on PMN at multiple levels, by promo ting their accumulation in tissues through the induction of chemotacti c factors (e.g. IL-8) and the upregulation of adhesion molecules, and by priming their response to chemotactic agonists.