EFFECTS OF TOPICAL ANTIINFLAMMATORY DRUGS ON EOSINOPHIL SURVIVAL PRIMED BY EPITHELIAL-CELLS - ADDITIVE EFFECT OF GLUCOCORTICOIDS AND NEDOCROMIL SODIUM

Background Eosinophil infiltration is a hallmark of the inflammatory r esponse in rhinitis and in nasal polyposis. Objective We studied the e ffect of steroids and nedocromil sodium on eosinophil survival primed by epithelial cells from healthy (nasal mucosa) and inflamed (nasal po lyp) respiratory tissue. Methods Blood eosinophils were incubated with increasing concentrations (10(-11)-10(-5) M) of topical steroids (flu ticasone propionate. budesonide, triamcinolone acetonide and beclometh asone dipropionate) and/or nedocromil sodium prior to the addition of human epithelial cell conditioned media (HECM), eosinophil viability w as measured and IC50 for each drug was calculated. Results All four st eroids and nedocromil sodium caused a dose-related inhibition of HECM- induced eosinophil survival. The IC50 Of steroids were lower in eosino phils primed by mucosa HECM than on those primed by polyp HECM (flutic asone, 4 nM vs 114 nM; budesonide, 21 nM vs 280 nM; triamcinolone, 7 n M vs 853 nM; and beclomethasone, 171 nM vs 181 nM). The combined inhib itory 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 budeson ide (52.3 +/- 11%). No differences were found in cytokine (IL-8, IL-6, GM-CSF, TNF alpha, IL-1 beta and RANTES) concentrations between HECM from mucosa and polyps. Conclusion These results suggest that topical anti-inflammatory drugs may diminish airway eosinophilic infiltration by decreasing eosinophil viability, that nasal polyp epithelial cell s ecretions may induce steroid resistance in eosinophils, and that nedoc romil sodium has additive effects with steroids.