CYTOKINES DIRECTLY INDUCE DEGRANULATION AND SUPEROXIDE PRODUCTION FROM HUMAN EOSINOPHILS

Background: Cytokines are implicated in allergic diseases and can modu late effector functions of eosinophils stimulated by another agonist. However, little is known about the capacity of cytokines to directly t rigger eosinophil degranulation. Objectives: We attempted to determine whether cytokines can directly induce degranulation and superoxide pr oduction from eosinophils. Methods: Eosinophils from normal donors wer e incubated with various cytokines in albumin coated tissue culture pl ates for 4 hours. To quantitate degranulation, the amounts of eosinoph il-derived neurotoxin in supernatants were measured by radioimmunoassa y. In addition, superoxide production was measure by superoxide dismut ase-inhibitable reduction of cytochrome c. Results: IL-5, IL-3, granul ocyte-macrophage colony-stimulating factor, tumor necrosis factor-alph a, and RANTES all induced eosinophil degranulation. Granulocyte-macrop hage colony-stimulating factor was the most potent and induced eosinop hil-derived neurotoxin release comparable to that induced by secretory IgA beads, one of the most potent secretagogues for eosinophils. In a ddition, IL-5 and tumor necrosis factor-alpha were synergistic in thei r induction of eosinophil degranulation. In contrast, IL-1, IL-8, inte rferon-gamma, and macrophage inflammatory protein-1 alpha did not indu ce degranulation. finally, IL-5, IL-3, granulocyte-macrophage colony-s timulating factor, and tumor necrosis factor-alpha, but not RANTES, al so induced superoxide production from eosinophils. Conclusions: Certai n cytokines directly induce eosinophil degranulation and superoxide pr oduction in vitro. Therefore these cytokines may be important in the r elease of toxic granule proteins from eosinophils in allergic diseases .