Shigeki Matsubara, Keiko Fushimi, Hideo Kikkawa, Kazuaki Naito and Katsuo
Ikezawa
Lead Optimization Research Laboratory, Tanabe Seiyaku, Co., Ltd., Toda,
Saitama 335-8505, Japan
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.
Keywords: Sephadex bead, Dexamethasone, Cyclosporin A, Eosinophil, Airway
hyperresponsiveness