Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion.
Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may be due to an effect on the release of epithelial cell products responsible for promoting eosinophil survival. We investigated the effect of fluticasone propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on eosinophil survival induced by secretions from cultured nasal epithelial cells. Human epithelial cell-conditioned media (HECM) were generated by cultured epithelial cells obtained from healthy subjects undergoing corrective nasal surgery. Normodense eosinophils isolated from peripheral blood were incubated with HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluticasone propionate had the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 13x10(-8) M), and nedocromil sodium (IC25 >10(-5) M). A significant correlation was found between both inhibitory effects (r=0.955; p<0.05). Topical anti-inflammatory drugs may decrease eosinophil survival by abrogating the promoting effect of epithelial cells. These drugs may exert part of their therapeutic effect by modulating GM-CSF release. The following rank of potency was observed: fluticasone propionate > budesonide > beclomethasone dipropionate > nedocromil sodium. The study of the interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.
Roca-Ferrer
J
J
Fundació Clinic per a la Recerca Biomèdica, Departament de Medicina, Universitat de Barcelona, Catalonia, Spain.
Mullol
J
J
Lopez
E
E
Xaubet
A
A
Pujols
L
L
Fernández
J C
JC
Picado
C
C
D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells; D005260:Female; D005938:Glucocorticoids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009297:Nasal Mucosa / Q000166:cytology*
D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D005938:Glucocorticoids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor