THE ROLE OF ENDOGENOUS CORTICOSTERONE IN THE LATE-PHASE RESPONSE TO ALLERGEN CHALLENGE IN THE BROWN-NORWAY RAT

The aim of this study was to assess the role of endogenous corticoster one (CCST) concentrations on the late airway response (LAR) to ovalbum in (OA). Thirty-two Brown Norway (BN) rats were sensitized to OA on Da y 0, then divided into three groups. Group 1 (n = 11) received saline (1 ml, subcutaneously) at time (T) = -24, -12, and 0 h prior to a 5% O A challenge on Day 14. Group 2 (n = 11) received metyrapone (MTP), an 11 beta-hydroxylase inhibitor, (10 mg/100 g in 1 ml saline, subcutaneo usly) at time (T) = -24, -12, and 0 h. Group 3 (n = 10) received MTP o n the same schedule as Group 2, plus CCST in the drinking water (16 mu g/ml) from T = -24 to T = 0 h. Pulmonary resistance (R(L)) was measur ed for 8 h following OA challenge to determine early (EAR) and LAR. Bl ood samples were taken at T = 0 and T = 8 h to determine serum CCST le vels. Bronchoalveolar lavage (BAL) fluid was collected at T = 8 h. Ser um CCST levels were significantly reduced in the MTP group (235 ng/ml +/- 14 SEM) compared with control (564 +/- 38, p < 0.0001) and MTP + C CST animals (349 +/- 19, p < 0.0005). There were no differences in eit her baseline R(L) or EAR between the groups. However, the MTP group ha d a smaller LAR (6 ml/cm H2O/smin +/- 2 SEM) than the control group ( 19 rt 5, p < 0.02). The effect of MTP on LAR was reversed by treatment with CCST (21 +/- 3, p < 0.005). Total cell counts (p < 0.05) and eos inophils (p < 0.01) were increased in the BAL fluid of MTP rats versus control and MTP + CCST animals. We conclude that depletion of endogen ous CCST in the BN rat diminishes the LAR to allergen challenge. These results indicate that physiologic levels of CCST are not necessary fo r development of the EAR, but they play a permissive role in the LAR t o inhaled allergen.