title: The role of endogenous corticosterone in the late-phase response to allergen challenge in the brown Norway rat.
abstract: The aim of this study was to assess the role of endogenous corticosterone (CCST) concentrations on the late airway response (LAR) to ovalbumin (OA). Thirty-two Brown Norway (BN) rats were sensitized to OA on Day 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% OA challenge on Day 14. Group 2 (n = 11) received metyrapone (MTP), an 11 beta-hydroxylase inhibitor, (10 mg/100 g in 1 ml saline, subcutaneously) at time (T) = -24, -12, and 0 h. Group 3 (n = 10) received MTP on the same schedule as Group 2, plus CCST in the drinking water (16 micrograms/ml) from T = -24 to T = 0 h. Pulmonary resistance (RL) was measured for 8 h following OA challenge to determine early (EAR) and LAR. Blood samples were taken at T = 0 and T = 8 h to determine serum CCST levels. Bronchoalveolar lavage (BAL) fluid was collected at T = 8 h. Serum CCST levels were significantly reduced in the MTP group (235 ng/ml +/- 14 SEM) compared with control (564 +/- 38, p < 0.0001) and MTP+CCST animals (349 +/- 19, p < 0.0005). There were no differences in either baseline RL or EAR between the groups. However, the MTP group had a smaller LAR (6 ml/cm H2O/s*min +/- 2 SEM) than the control group (19 +/- 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 eosinophils (p < 0.01) were increased in the BAL fluid of MTP rats versus control and MTP+CCST animals. We conclude that depletion of endogenous CCST in the BN rat diminishes the LAR to allergen challenge. These results indicate that physiologic levels of CCST are not necessary for development of the EAR, but they play a permissive role in the LAR to inhaled allergen.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Québec, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Turner
authors.forename: P
authors.initials: P
authors.lastname: Myron
authors.forename: W S
authors.initials: WS
authors.lastname: Powell
authors.forename: J G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D000403:Airway Resistance; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000276:immunology / Q000502:physiology*; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007114:Immunization; D008797:Metyrapone / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors
chemical_list: D000485:Allergens; D010047:Ovalbumin; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone; D008797:Metyrapone