Cytokines directly induce degranulation and superoxide production from human eosinophils

Background: Cytokines are implicated in allergic diseases and can modulate effector functions of eosinophils stimulated by another agonist. However, little is known about the capacity of cytokines to directly trigger eosinophil degranulation. Objectives: We attempted to determine whether cytokines can directly induce degranulation and superoxide production from eosinophils. Methods: Eosinophils from normal donors were incubated with various cytokines in albumin coated tissue culture plates for 4 hours. To quantitate degranulation, the amounts of eosinophil-derived neurotoxin in supernatants were measured by radioimmunoassay. In addition, superoxide production was measure by superoxide dismutase-inhibitable reduction of cytochrome c. Results: IL-5, IL-3, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and RANTES all induced eosinophil degranulation. Granulocyte-macrophage colony-stimulating factor was the most potent and induced eosinophil-derived neurotoxin release comparable to that induced by secretory IgA beads, one of the most potent secretagogues for eosinophils. In addition, IL-5 and tumor necrosis factor-alpha were synergistic in their induction of eosinophil degranulation. In contrast, IL-1, IL-8, interferon-gamma, and macrophage inflammatory protein-1 alpha did not induce degranulation. finally, IL-5, IL-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, but not RANTES, also induced superoxide production from eosinophils. Conclusions: Certain cytokines directly induce eosinophil degranulation and superoxide production in vitro. Therefore these cytokines may be important in the release of toxic granule proteins from eosinophils in allergic diseases.