title: Budesonide down-regulates eosinophil locomotion but has no effects on ECP release or on H2O2 production.
abstract: Treatment of allergic asthma with inhaled corticosteroids results in local down-regulation of proinflammatory cytokine synthesis and in marked decrease in tissue eosinophilia. Blood concentrations of inhaled corticosteroids, although significantly lower than those measured in the lung, may still have antiinflammatory effects on circulating eosinophils, reducing their ability to migrate. The aim of our study was to evaluate in vitro the activity of budesonide on blood eosinophils by measuring their chemotactic response, eosinophil cationic protein (ECP) release, and hydrogen peroxide (H2O2) production in the presence of different drug concentrations similar to those obtained at airway level (10(-8) and 10(-7) M) and at blood level (10(-10) and 10(-9) M). Partially purified blood eosinophils, isolated from 23 asthmatic subjects, were used to evaluate the activity of budesonide on: (1) chemotaxis toward the activated fifth component of complement (C5a, 0.1 microg/ml) or recombinant human (rh) interleukin (IL)-5 (200 pg/ml), (2) ECP release by cells stimulated with tetradecanoylphorbol acetate (TPA) and (3) H2O2 production by TPA-activated cells. The chemotactic response to C5a was down-regulated significantly by budesonide only by the highest concentrations tested (10(-8) and 10(-7) M); differently, budesonide was effective in inhibiting eosinophil migration toward rhIL-5, at all concentrations tested (p < 0.01, each comparison). By contrast, no drug-induced modifications were observed in ECP release or in H2O2 production (p > 0.05, each comparison). We conclude that concentrations of budesonide similar to those obtained in vivo are effective in inhibiting eosinophil locomotion but not in down-regulating the release of reactive oxygen species and granule-associated proteins.
authors.affiliation: Pulmonary Division, G. Gaslini Institute, Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lantero
authors.forename: S
authors.initials: S
authors.lastname: Oddera
authors.forename: M
authors.initials: M
authors.lastname: Silvestri
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez Rodriguez
authors.forename: M C
authors.initials: MC
authors.lastname: Morelli
authors.forename: G A
authors.initials: GA
authors.lastname: Rossi
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000276:immunology; D001798:Blood Proteins / Q000378:metabolism; D019819:Budesonide / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D012260:Ribonucleases
chemical_list: D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D018836:Inflammation Mediators; D019819:Budesonide; D006861:Hydrogen Peroxide; D012260:Ribonucleases