THE EFFECTS OF INTERLEUKIN-8 ON NEUTROPHIL FMETLEUPHE RECEPTORS, CD11B EXPRESSION AND METABOLIC-ACTIVITY, IN COMPARISON AND COMBINATION WITH OTHER CYTOKINES

The effect of the chemotactic cytokine, IL-8, on neutrophil function w as compared with that of other cytokines, GM-CSF, G-CSF TNFalpha and I FN-gamma. IL-8 rapidly stimulated a three-fold enhancement of the fMLP -stimulated respiratory burst, but this priming effect was transient c ompared with the slower and sustained effects of GM-CSF and IFNgamma. Apart from G-CSF, IL-8 was the weakest priming agent and was weaker th an GM-CSF in priming arachidonic acid metabolism stimulated by calcium ionophore. When incubated in combination. IL-8 and TNFalpha were high ly synergistic in their effects on respiratory burst priming, whereas IL-8 and GM-CSF showed little synergy. In contrast. IL-8 was as potent as GM-CSF at increasing the expression of neutrophil chemotactic pept ide receptors and the beta2 integrin, CD11b. The latter was maximally upregulated within 5 min of stimulation with IL-8, whereas the effect of GM-CSF was much slower. The kinetics of neutrophil respiratory burs t priming by IL-8 were the same when measured in whole blood samples a nd in purified cell suspensions, and IL-8 dose-response curves were si milar, showing that the low affinity IL-8 receptors on erythrocytes do not rapidly sequester circulating IL-8. The data suggest that IL-8 pl ays a minor role in priming neutrophil function and that a more major activity is the regulation of neutrophil adhesion and migration.