STIMULATION AND PRIMING OF HUMAN NEUTROPHILS BY IL-1-ALPHA AND IL-1-BETA - COMPLETE INHIBITION BY IL-1 RECEPTOR ANTAGONIST AND NO INTERACTION WITH OTHER CYTOKINES

Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O-2(-)) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each trig gered O-2(-) release in a dose-dependent manner. The maximal priming a nd triggering effect was obtained by high concentrations (50 to 500 ng /mL) of IL-1 alpha or IL-1 beta, though IL-1 beta was more effective t han IL-1 alpha at suboptimal concentrations. Priming effect of IL-1 wa s very rapid and maximal within 10 minutes, whereas O-2(-) release tri ggered by IL-1 was gradual and continued for 90 to 120 minutes. Combin ed stimulation of human neutrophils with IL-1 plus granulocyte colony- stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) resu lted in additive priming effect, and combined stimulation of neutrophi ls with IL-1 plus G-CSF, GM-CSF, or tumor necrosis factor (TNF) result ed in additive triggering effect, even when the maximal concentration of each cytokine was used. These priming and triggering effects of IL- 1 alpha and IL-1 beta on the respiratory burst in human neutrophils we re completely inhibited by IL-1 receptor antagonist (IL-1ra). Furtherm ore, only the net effect of IL-1 was inhibited by IL-1ra, even when hu man neutrophil was stimulated with IL-1 plus other cytokines to releas e O-2(-). Present results indicate that IL-1 does stimulate the respir atory burst activity in human neutrophils via receptor-mediated mechan ism and suggest that the post-IL-1-receptor signaling pathways linked to the activation system of the respiratory burst are independent from those utilized by other cytokines in human neutrophils.