Glucocorticoids inhibit granulocyte-macrophage colony-stimulating factor-1 and interleukin-5 enhanced in vitro survival of human eosinophils.
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.
Hallsworth
M P
MP
Department of Allergy and Allied Respiratory Disorders, U.M.D.S., Guy's Hospital, London, U.K.
Litchfield
T M
TM
Lee
T H
TH
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D008775:Methylprednisolone / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D005938:Glucocorticoids; D015848:Interleukin-5; D011994:Recombinant Proteins; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006854:Hydrocortisone; D008775:Methylprednisolone