Effects of topical anti-inflammatory drugs on eosinophil survival primed by epithelial cells. Additive effect of glucocorticoids and nedocromil sodium.
BACKGROUND
Eosinophil infiltration is a hallmark of the inflammatory response in rhinitis and in nasal polyposis.


OBJECTIVE
We studied the effect of steroids and nedocromil sodium on eosinophil survival primed by epithelial cells from healthy (nasal mucosa) and inflamed (nasal polyp) respiratory tissue.


METHODS
Blood eosinophils were incubated with increasing concentrations (10(-11)-10(-5) M) of topical steroids (fluticasone propionate, budesonide, triamcinolone acetonide and beclomethasone dipropionate) and/or nedocromil sodium prior to the addition of human epithelial cell conditioned media (HECM), eosinophil viability was measured and IC50 for each drug was calculated.


RESULTS
All four steroids and nedocromil sodium caused a dose-related inhibition of HECM-induced eosinophil survival. The IC50 of steroids were lower in eosinophils primed by mucosa HECM than on those primed by polyp HECM (fluticasone, 4 nM vs 114 nM; budesonide, 21 nM vs 280 nM; triamcinolone, 7 nM vs 853 nM; and beclomethasone, 171 nM vs 181 nM). The combined inhibitory effect of 10(-7) M budesonide plus 10(-5) M nedocromil (43.8 +/- 10.8%, P<0.03) was significantly higher than budesonide (28.5 +/- 9.2%) or nedocromil (16.7 +/- 5.4%) alone and close to 10(-5) M budesonide (52.3 +/- 11%). No differences were found in cytokine (IL-8, IL-6, GM-CSF, TNF alpha, IL-1beta and RANTES) concentrations between HECM from mucosa and polyps.


CONCLUSIONS
These results suggest that topical anti-inflammatory drugs may diminish airway eosinophilic infiltration by decreasing eosinophil viability, that nasal polyp epithelial cell secretions may induce steroid resistance in eosinophils, and that nedocromil sodium has additive effects with steroids.
Mullol
J
J
Fundació Clínic per a la Recerca Biomèdica, Hospital Clínic i Universitari, Departament de Medicina, Universitat de Barcelona, Spain.
López
E
E
Roca-Ferrer
J
J
Xaubet
A
A
Pujols
L
L
Fernàndez-Morata
J C
JC
Fabra
J M
JM
Picado
C
C
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017835:Nedocromil / Q000008:administration & dosage / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D005938:Glucocorticoids; D017835:Nedocromil