title: Difference in inhibitory effects of dexamethasone and cyclosporin A on Sephadex bead-induced airway hyperresponsiveness and inflammation in rats.
abstract: We investigated the effects of dexamethasone and cyclosporin A on Sephadex bead (Sephadex G-200, Sephadex)-induced airway hyperresponsiveness (AHR) and inflammation in rats. Sephadex (0.5 mg/animal) was intravenously administered on days 0, 2 and 5. Bronchoalveolar lavage, histological study and measurement of AHR were performed on day 7. Dexamethasone (0.1, 1 and 10 mg/kg, p.o. x 3) and cyclosporin A (0.1, 1 and 10 mg/kg, s.c. x 3) clearly inhibited the increase in eosinophils in bronchoalveolar lavage fluid after Sephadex injection. On histological study, pulmonary eosinophilia, granulomatous arteritis with horseshoe-shaped multinuclear giant cell formation and goblet hyperplasia were observed after Sephadex injection. Both dexamethasone (10 mg/kg x 3) and cyclosporin A (10 mg/kg x 3) inhibited these findings and an increase in eosinophil peroxidase in the lung. Dexamethasone dose-dependently inhibited AHR induced by Sephadex, and completely suppressed it at a dose of 1 mg/kg (x 3). Cyclosporin A, however, did not inhibit AHR even at a dose of 10 mg/kg ( x 3). These results show that there is a difference between dexamethasone and cyclosporin A in the inhibitory effect on Sephadex-induced AHR, and they suggest that eosinophils are not directly associated with the development of AHR after Sephadex injection.
authors.affiliation: Lead Optimization Research Laboratory, Tanabe Seiyaku, Co., Ltd., Toda, Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsubara
authors.forename: K
authors.initials: K
authors.lastname: Fushimi
authors.forename: H
authors.initials: H
authors.lastname: Kikkawa
authors.forename: K
authors.initials: K
authors.lastname: Naito
authors.forename: K
authors.initials: K
authors.lastname: Ikezawa
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D001991:Bronchitis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D003911:Dextrans / Q000633:toxicity*; D004789:Enzyme Activation; D047209:Eosinophil Peroxidase; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D003911:Dextrans; D003907:Dexamethasone; D016572:Cyclosporine; C025614:sephadex; D047209:Eosinophil Peroxidase; D010544:Peroxidases