FLUTICASONE PROPIONATE ATTENUATES OZONE-INDUCED RHINITIS AND MUCOUS CELL METAPLASIA IN RAT NASAL AIRWAY EPITHELIUM

Ozone (O-3) is the principal oxidant pollutant in photochemical smog. Repeated exposures to O-3 induces inflammation and mucous cell metapla sia in the nasal airways of laboratory animals. Our study was designed to determine the efficacy of a topical anti-inflammatory corticostero id in preventing O-3-induced rhinitis and mucous cell metaplasia in ra t nasal epithelium. Male F344 rats were exposed to filtered air (O ppm O-3; air-controls) or 0.5 ppm O-3, 8 h/day, for 3 or 5 days. Immediat ely before and after each exposure, rats received an intranasal instil lation (50 mu l/nasal passage) of a topical corticosteroid, fluticason e propionate (FP; 25 mu g/nasal passage) or its vehicle only (0.01% et hanol in saline). Rats were killed 2 h after the third exposure (3-day exposure) or 3 days after the fifth exposure (5-day exposure) and nas al tissues were processed for light microscopy. Numeric densities of e pithelial cells and neutrophils, and the amount of intraepithelial muc osubstances (IM) in the epithelium lining the maxilloturbinates were m orphometrically determined. There were no significant differences in a ny measured parameter in air-exposed rats instilled with FP compared w ith air-exposed rats instilled with vehicle. Vehicle-treated rats expo sed to ozone had neutrophilic rhinitis with 3.3 and 1.6-fold more intr aepithelial neutrophils (3-day and 5-day exposure, respectively) and m arked mucous cell metaplasia (5-day exposure only) with numerous mucou s cells and approximately 60 times more IM in the nasal transitional e pithelium compared with vehicle-treated air controls. FP-treated rats exposed to ozone had minimal nasal inflammation (1.3-fold more intraep ithelial neutrophils only after 3-day exposure) and minimal mucous cel l metaplasia (5-fold more IM only after 5-day exposure) compared with vehicle-instilled, air-exposed rats. Results of this study indicate th at FP-treatment is effective in attenuating not only O-3-induced rhini tis (30-60% reduction) but also O-3-induced mucous cell metaplasia (85 % reduction) in rat nasal transitional epithelium. The cellular and mo lecular mechanisms involved in FP-induced attenuation of O-3-induced n asal lesions remain to be determined.