Glucocorticoids inhibit cytokine-mediated eosinophil survival.

摘要: Glucocorticoids characteristically induce eosinopenia in vivo and are effective for treating allergic other eosinophilic disorders. We studied the effect of glucocorticoids on cytokine-induced survival human eosinophils vitro. Eosinophils were purified from normal or mildly atopic volunteers by Percoll density gradient incubated 4 days presence cytokine plus steroid. Cell viabilities determined staining cells with fluorescein diacetate propidium iodide. In absence glucocorticoids, rIL-5 enhanced eosinophil a dose-dependent manner, 22 fM minimal to 2200 maximal effect. When cultured submaximal concentration (220 fM), dexamethasone, methylprednisolone, hydrocortisone inhibited manner. Inhibition was time-dependent required at least 2 days' exposure dexamethasone. Dexamethasone, 1000 nM 88 +/- 2, 66 9 37 7%. contrast, estradiol testosterone (1000 nM) had no survival. varying concentrations inhibition reduced higher rIL-5, completely abolished 23,000 fM. Human recombinant granulocyte-macrophage CSF, rIL-3, rIFN-gamma also manner dexamethasone strongly cell when these cytokines used. The effects reversed CSF (10 U/ml) IL-3 (3 ng/ml). However, even U/ml IFN-gamma did not overcome inhibition, indicating difference between mechanism induced cytokines. These results suggest that exert direct, inhibitory survival, which may be important treatment Antagonism this amounts glucocorticoid resistance.