EFFECT OF DEXAMETHASONE AND ENDOGENOUS CORTICOSTERONE ON AIRWAY HYPERRESPONSIVENESS AND EOSINOPHILIA IN THE MOUSE

1 Mice were sensitized by 7 intraperitoneal injections of ovalbumin wi thout adjuvant (10 mu g in 0.5 ml of sterile saline) on alternate days and after 3 weeks exposed to either ovalbumin (2 mg ml(-1) in sterile saline) or saline aerosol for 5 min on 8 consecutive days. One day be fore the first challenge, animals were injected intraperitoneally on a daily basis with vehicle (0.25 ml sterile saline), dexamethasone (0.5 mg kg(-1)) or metyrapone (30 mg kg(-1)). 2 In vehicle-treated ovalbum in-sensitized animals ovalbumin challenge induced a significant increa se of airway responsiveness to metacholine both in vitro (27%, P <0.05 ) and in vivo (40%, P <0.05) compared to saline-challenged mice. Virtu ally no eosinophils could be detected after saline challenge, whereas the numbers of eosinophils were significantly increased (P <0.01) at b oth 3 and 24 h after the last ovalbumin challenge (5.48+/-3.8x10(3) an d 9.13+/-1.7x10(3) cells, respectively). Furthermore, a significant in crease in ovalbumin-specific immunoglobulin E level (583+/-103 units m l(-1), P <0.05) was observed after ovalbumin challenge compared to sal ine challenge (201+/-38 units ml(-1)). 3 Plasma corticosterone level w as significantly reduced (-92%, P <0.001) after treatment with metyrap one. Treatment with metyrapone significantly increased eosinophil infi ltration (17.4+/-9.93x10(3) and 18.7+/-2.57x10(3) cells, P <0.05 at 3 h and 24 h, respectively) and potentiated airway hyperresponsiveness t o methacholine compared to vehicle-treated ovalbumin-challenged animal s. Dexamethasone inhibited both in vitro and in vivo hyperresponsivene ss as well as antigen-induced infiltration of eosinophils (0, P <0.05 and 0.7+/-0.33x10(3) cells, P <0.05; at 3 h and 24 h, respectively). M etyrapone as well as dexamethasone did not affect the increase in oval bumin-specific immunoglobulin E levels after ovalbumin challenge (565/-70 units/ml(-1); P<0.05; 552+/-48 units ml(-1), P <0.05 respectively ). 4 From these data it can be concluded that exogenously applied cort icosteroids can inhibit eosinophil infiltration as well as airway hype rresponsiveness. Vise versa, endogenously produced corticosteroids pla y a down-regulating role on the induction of both eosinophil infiltrat ion and airway hyperresponsiveness.