Glucocorticoids inhibit granulocyte-macrophage colony-stimulating factor-1 and interleukin-5 enhanced in vitro survival of human eosinophils. 1992

M P Hallsworth, and T M Litchfield, and T H Lee
Department of Allergy and Allied Respiratory Disorders, U.M.D.S., Guy's Hospital, London, U.K.

The effects of three corticosteroids, hydrocortisone, dexamethasone and methylprednisolone, on eosinophil survival enhanced by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant murine interleukin-5 (rmIL-5) have been studied. Eosinophils were incubated at a concentration of 5 x 10(5) cells/ml in the presence of different concentrations of the three steroids with either rhGM-CSF (1 ng/ml) or rmIL-5 (50 U/ml). The eosinophils were cultured in the presence of the same concentrations of rhGM-CSF and rmIL-5 alone as a positive control and medium alone as a negative control. Viability was assessed after 7 days by trypan blue exclusion. All three steroids inhibited rhGM-CSF-enhanced eosinophil survival in a dose-dependent manner; the dose of these drugs producing 50% inhibition (IC50) was greater than 1.0 x 10(-4) M, 6.5 x 10(-6) M and 1.8 x 10(-6) M for hydrocortisone, dexamethasone and methylprednisolone, respectively. When eosinophils were cultured with the same concentration of rhGM-CSF in the presence of two non-glucocorticoids, beta-oestradiol and testosterone, neither of these steroids inhibited eosinophil survival over the concentration range 1 x 10(-10) M to 1 x 10(-4) M (n = 5). Dexamethasone and methylprednisolone, but not hydrocortisone, also inhibited eosinophil survival induced by rmIL-5 in a dose-dependent manner. These results suggest one mechanism for the efficacy of corticosteroids against eosinophil-related disorders.

UI MeSH Term Description Entries
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004804 Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Eosinophil
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006854 Hydrocortisone The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol

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