Eosinophil activation in the tissue: synthetic steroid, budesonide, effectively inhibits the survival of eosinophils isolated from peripheral blood but not nasal polyp tissues.
We investigated the effect of a potent synthetic steroid, budesonide (BUD), on the survival of nasal polyp (NP) derived eosinophils (EOS). BUD, at the highest dose used, 10(-6) M, decreased this survival but only by approximately one third. We speculated that the relatively small inhibitory effect of budesonide on the survival of NP-EOS could be the result of these EOS being exposed to substantial amounts of GM-CSF, IL-5 or IL-3. In this regard, we detected 148 pg of GM-CSF per 150 mg of tissue, which approximately contained 106 of eosinophils, in the supernatant of NP explants for 24 h without any stimulation. Contents of both IL-5 and IL-3 were much less. We further studied survival of PB-EOS exposed to rhGM-CSF and found that 10(-6) M of BUD could only inhibit by less than one third the survival of PB-EOS exposed to an amount of rhGM-CSF, similar to that detected in the supernatant of NP explants. In addition, we exposed PB-EOS to 200 pg/ml of rhGM-CSF for a relatively long period of time (4 days) in order to mimic chronic exposure in the tissue and found that the survival of these cells was prolonged to the extent similar to that observed in NP-EOS. Our data suggests that the prolonged spontaneous survival of NP-EOS ex vivo is likely the result of sustained in vivo exposure to GM-CSF and budesonide has a smaller inhibitory effect in the survival of these eosinophils as compared to those from peripheral blood.
Nonaka
R
R
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Nonaka
M
M
Takanashi
S
S
Jordana
M
M
Dolovich
J
J
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004347:Drug Interactions; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009298:Nasal Polyps / Q000473:pathology* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D011994:Recombinant Proteins; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor