Glucocorticoids inhibit cytokine-mediated eosinophil survival

• Published in: The Journal of immunology (1950) Vol. 147; no. 10; pp. 3490 - 3495
• Main Authors: Wallen, N, Kita, H, Weiler, D, Gleich, GJ
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.11.1991; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cell Survival - drug effects; Cytokines - pharmacology; Dexamethasone - pharmacology; Eosinophils - cytology; Eosinophils - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glucocorticoids - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Humans; Hydrocortisone - pharmacology; Immunobiology; In Vitro Techniques; Interferon-gamma - pharmacology; Interleukin-3 - pharmacology; Interleukin-5 - pharmacology; Methylprednisolone - pharmacology; Miscellaneous; Regulatory factors and their cellular receptors; Human; Corticosteroid; Dexamethasone; Cytokine; Glucocorticoid; Survival; Eosinophil; Interleukin 5; Interleukin 3; Inhibition; Mechanism of action; Granulocyte macrophage colony stimulating factor; Gamma interferon
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.147.10.3490

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