Interleukin-8 primes human neutrophils for enhanced superoxide anion production

Interleukin-8 (IL-8), a novel chemotactic cytokine, has been shown to play an important role in inflammation. In this study, we investigated the effect of recombinant human (rh) IL-8 on superoxide (O2-) production by neutrophils. We found that rhIL-8 (1-10 ng/ml) did not stimulate neutrophil O2- production on its own, but primed neutrophils for an enhanced response to other stimuli, such as N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol 12-myristate 13-acetate (PMA) and platelet-activating factor (PAF). The priming effect of rhIL-8 was dose dependent, rapid and long lasting. Recombinant human IL-8 increased both the maximal rate and the total O2- production, but did not prolong the response to FMLP. Stimulation of neutrophils with rhIL-8 increased intracellular-free calcium concentration ([Ca2+]i) by mobilizing calcium from internal stores and by increasing calcium influx. The increase in [Ca2+]i was dose dependent and occurred in the same range of rhIL-8 concentrations that primed neutrophils for O2- production. In addition, rhIL-8 enhanced the FMLP-stimulated increase in [Ca2+]i. These observations suggest that calcium may play an important role in priming phenomenon.