title: 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.
abstract: Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and 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 than IL-1 alpha at suboptimal concentrations. Priming effect of IL-1 was very rapid and maximal within 10 minutes, whereas O2- release triggered by IL-1 was gradual and continued for 90 to 120 minutes. Combined stimulation of human neutrophils with IL-1 plus granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) resulted in additive priming effect, and combined stimulation of neutrophils with IL-1 plus G-CSF, GM-CSF, or tumor necrosis factor (TNF) resulted 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 were completely inhibited by IL-1 receptor antagonist (IL-1ra). Furthermore, only the net effect of IL-1 was inhibited by IL-1ra, even when human neutrophil was stimulated with IL-1 plus other cytokines to release O2-. Present results indicate that IL-1 does stimulate the respiratory burst activity in human neutrophils via receptor-mediated mechanism 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.
authors.affiliation: Research Institute, International Medical Center of Japan, Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Yagisawa
authors.forename: A
authors.initials: A
authors.lastname: Yuo
authors.forename: S
authors.initials: S
authors.lastname: Kitagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: A
authors.initials: A
authors.lastname: Togawa
authors.forename: F
authors.initials: F
authors.lastname: Takaku
mesh_terms: D000328:Adult; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D016897:Respiratory Burst / Q000187:drug effects*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D017472:Receptors, Interleukin-1