Effect of steroids on immunoglobulin-induced eosinophil degranulation.
Because glucocorticoids are a mainstay in the treatment of asthma and other allergic diseases, we tested the effect of various steroid hormones on secretory IgA- and IgG-induced eosinophil degranulation in vitro. Human normodense eosinophils were purified by discontinuous Percoll density gradient, and hypodense eosinophils were obtained by culture of normodense cells with recombinant human interleukin (rIL)-5. Eosinophils were incubated with various steroids, including dexamethasone, hydrocortisone, methylprednisolone, estradiol, or dihydrotestosterone at concentrations from 10(-9) to 10(-4) mol/L. Sepharose 4B beads coupled to ovalbumin, secretory IgA, or IgG were added as targets of degranulation and incubated at 37 degrees C for 4 hours. In some experiments, rIL-5 was added to eosinophils before addition of beads to activate the cells. The release of eosinophil-derived neurotoxin was measured by radioimmunoassay as an index of degranulation. Dexamethasone (10(-9) to 10(-4) mol/L), hydrocortisone (10(-9) to 10(-4) mol/L), estradiol (10(-9) to 10(-7) mol/L), and dihydrotestosterone (10(-9) to 10(-4) mol/L) had no effect on normodense eosinophil degranulation. Methylprednisolone, 10(-5) mol/L, inhibited degranulation of normodense eosinophils up to 20%, whereas 10(-4) mol/L inhibited degranulation of hypodense eosinophils, up to 30%. Overall, no difference in inhibition by steroids was observed between normodense and hypodense eosinophils. rIL-5 enhanced immunoglobulin-induced eosinophil degranulation, but this effect of rIL-5 was not blocked by any of the steroids tested. These results suggest that eosinophil degranulation and rIL-5-mediated eosinophil activation are not direct targets of glucocorticoids and that the beneficial effects of glucocorticoids on allergic inflammation in vivo are not likely due to direct effects on eosinophil degranulation.
Kita
H
H
Department of Immunology, Mayo Clinic, Rochester, Minn. 55905.
Abu-Ghazaleh
R
R
Sanderson
C J
CJ
Gleich
G J
GJ
D015550:Cell Degranulation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004804:Eosinophils / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007070:Immunoglobulin A / Q000502:physiology; D007071:Immunoglobulin A, Secretory / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology; D007136:Immunoglobulins / Q000502:physiology*; D008775:Methylprednisolone / Q000494:pharmacology; D011863:Radioimmunoassay
D005938:Glucocorticoids; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007136:Immunoglobulins; D013196:Dihydrotestosterone; D003907:Dexamethasone; D006854:Hydrocortisone; D008775:Methylprednisolone