Inhaled budesonide decreases airway inflammatory response to allergen

To define the mechanisms by which inhaled glucocorticosteroid regulates all ergen-induced airway inflammation, a double-blind, placebo-controlled, cros s-over study with inhaled budesonide was conducted in 14 subjects with alle rgic asthma. After baseline bronchoscopy and bronchoalveolar lavage (BAL), subjects were randomized to budesonide (400 mu g, twice daily) or placebo t reatment for 4 wk. At the end of each treatment phase, whole-lung allergen inhalation challenge was performed, followed by BAL 48 h later. Budesonide treatment improved the FEV1, attenuated both the immediate- and late-phase response to allergen, and prevented the increase in bronchial hyperresponsi veness after allergen challenge. Budesonide treatment also decreased allerg en-induced airway eosinophilia. To determine the effects of budesonide on a irway cell function, BAL cells were stimulated ex vivo with the T cell mito gen PHA, and cytokine generation was measured by ELISA. Budesonide decrease d ex vivo generation of IL-5 and IFN-gamma by BAL cells. Ex vivo IL-5 produ ction was significantly correlated with the number of airway eosinophils (r (s) = 0.61), and levels of eosinophil-derived neurotoxin (EDN) (r(s) = 0.57 ) and IL-5 (r(s) = 0.52) in BAL fluid. Moreover, PHA-induced IL-5 generatio n correlated with FEV1 fall during the late-phase response to allergen (r(s ) = 0.60). Budesonide decreased circulating eosinophils and serum levels of IL-5, but did not reduce IL-5 generation by peripheral blood mononuclear c ells. The reduction in circulating eosinophils correlated with the decrease in levels of EDN (r(s) = 0.61) in BAL fluid and late response to inhaled a llergen (r(s) = 0.51). These findings suggest that long-term treatment with inhaled budesonide reduces airway cell generation of cytokines, specifical ly IL-5, which then decreases circulating eosinophils and their availabilit y for recruitment to the airway after allergen exposure.