FLUTICASONE PROPIONATE AND PENTAMIDINE ISETHIONATE REDUCE AIRWAY HYPERREACTIVITY, PULMONARY EOSINOPHILIA AND PULMONARY DENDRITIC CELL RESPONSE IN A GUINEA-PIG MODEL OF ASTHMA

In this study, we examined the effects of fluticasone propionate (FP) and pentamidine isethionate (PI) on antigen-induced lung inflammation and airway hyperreactivity in guinea pigs. Male guinea pigs were sensi tized on days 0 and 14 with 10 mu g of ovalbumin (OVA) plus 1 mg of Al (OH)(3). On day 21, animals were challenged with a 2% OVA aerosol inha lation until they developed pulmonary obstruction. Animals were treate d with aerosol inhalation of FP (2 ml of 0.5 mg/ml, five consecutive d oses at 12-hr intervals with the last dose given 6 hr before OVA chall enge) or PI (30 mg/ml for 30 min 1 hr before OVA challenge), and contr ol animals received no drug before OVA challenge. Airway reactivity to methacholine (MCh) was assessed before sensitization and 18 hr after OVA challenge. At 18 hr after challenge, histological sections of trac hea and lung were examined for eosinophil, dendritic cell (DC) and mac rophage cell densities in the airways. in control animals, OVA evoked airway hyperreactivity to MCh in conjunction with pulmonary eosinophil ia and increases in DG prevalence in the trachea and bronchi. Treatmen t with FP or PI abolished the OVA-induced hyperresponsiveness and sign ificantly reduced the OVA-induced increases in eosinophils and DCs in the airways. FP and PI had no effect on saline-treated animals. Our st udy indicates that both inhaled FP and inhaled PI reduce antigen-induc ed airway hyperreactivity and pulmonary inflammation in guinea pigs. T he results also suggest that the DC is a target of the anti-inflammato ry effects of these drugs in the airways.