The Interaction of Cytokine and Glucocorticoid in the Programmed Cell Death of Eosinophils

다국어 초록 (Multilingual Abstract)

The in vitro viability and the physical and functional phenotype of human peripheral blood eosinophils are regulated by the action of granulocyte-macrophage colony-stimulating factor(GM -CSF), interleukin-3(IL-3), and IL-5. In the idiopathic hypereosinophils syndrome and the tryptophan-associated eosinophilia/myalgia syndrome, the presence of hypodence eosinophils in the blood is associated with excessive serum levels of IL-5. The aim of study was to characterize, and to utilize this model cell system to determine the endothelial cell-mediated interactions of IL-1 and dexamethasone on eosinophil viability. GMCSF was established as the constitutive and elicited human umbilical vein endothelial cell-derived eosinophil viability-sustaining factor. Stimulation of endothelium cell monolayers with interleukin-1 (IL-1 ; 5 U/ml) increased the 48-h elaboration of GM-CSF from a mean of 3.2 to a mean of 8.2 pM(p <0.05). Dexamethasone(100 nM) decreased the constitutive GM-CSF elaboration by 49%(p<0.001) but did not diminish production by IL-1-stimulated endothelium. However, eosinophil viability decreased by 21% in dexamethasone-pretreated IL-l-stimulated endothelial cell-conditioned medium(p <0.05), which suggested viability antagonism by glucocorticoids. After 24h of culture, eosinoph1 l viability for replicate cells in enriched medium alone or with l pm GM -CSF decreased from means of 43 and 75 % to means of 21 and 54%, respectively, when dexamethasone was induced(p <0.05). However, 10 pM GM-CSF, IL-3, or IL-5 protected the cells against dexamethasone and against endonucleasesspecific DNA fragmentation. In this model system of eosinophil-tissue interactions, dexamethasone prevents the endothelial cells from inducing a pathologic phenotypic change in the eosinophil by suppression of GM-CSF elaboration to concentration that are not cytoprotective. Cytokine priming by GM-CSF, IL-3, or IL-5 may account for the differential responsiveness of eosinophillic disorders to glucocorticoids.