Budesonide down-regulates eosinophil locomotion but has no effects on ECP release or on H2O2 production

Treatment of allergic asthma with inhaled corticosteroids results in local down-regulation of proinflammatory cytokine synthesis and in marked decreas e in tissue eosinophilia. Blood concentrations of inhaled corticosteroids, although significantly lower than those measured in the lung, may still hav e antiinflammatory effects on circulating eosinophils, reducing their abili ty to migrate. The aim of our study was to evaluate in vitro the activity o f budesonide on blood eosinophils by measuring their chemotactic response, eosinophil cationic protein (ECP) release, and hydrogen peroxide (H2O2) pro duction in the presence of different drug concentrations similar to those o btained at airway level (10(-8) and 10(-7) M) and at blood level (10(-10) a nd 10(-9) M), Partially purified blood eosinophils, isolated from 23 asthma tic subjects, were used to evaluate the activity of budesonide on: (1) chem otaxis toward the activated fifth component of complement (C5a, 0.1 mu g/ml ) or recombinant human (rh) interleukin (IL)-5 (200 pg/ml), (2) ECP release by cells stimulated with tetradecanoylphorbol acetate (TPA) and (3) H2O2 p roduction by TPA-activated cells. The chemotactic response to C5a was down- regulated significantly by budesonide only by the highest concentrations te sted (10(-8) and 10(-7) M); differently, budesonide was effective in inhibi ting eosinophil migration toward rhIL-5, at all concentrations tested (p < 0.01, each comparison). By contrast, no drug-induced modifications were obs erved in ECP release or in H2O2 production (p > 0.05, each comparison). We conclude that concentrations of budesonide similar to those obtained in viv o are effective in inhibiting eosinophil locomotion but not in down-regulat ing the release of reactive oxygen species and granule-associated proteins.