Allergen-induced late-phase airways obstruction in the pig: the role of endogenous cortisol

Abstract

In developing a novel model for studies of the allergen-induced late-phase airways obstruction, by using the pig, the importance of endogenous cortisol levels was examined by the use of metyrapone, a cortisol-synthesis inhibitor. Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen. One group of pigs was treated with a constant infusion of metyrapone in order to maintain low levels of plasma cortisol. Ascaris suum allergen was nebulized into the lower airways and plasma cortisol and catecholamine levels, total lung resistance and dynamic compliance, blood gases and pH, and blood flow in the bronchial circulation were continuously recorded for 8 h. At the time of allergen challenge, the plasma cortisol levels in sensitized pigs were 455 +/- 37 nM and 40.1 +/- 3.8 nM in non-metyrapone-treated and metyrapone-treated pigs, respectively. No difference was seen between the magnitude of the acute bronchoconstrictor response in the two groups. A late airways obstruction, starting at about 4 h, developed only in pigs with low cortisol levels, whereas a late increase in blood flow in the bronchial circulation was seen in both groups, even if a late airways obstruction was absent. Plasma adrenaline did not seem to influence the late-phase reaction. These results suggest that endogenous cortisol levels, but not adrenaline, modify the late response to allergen in the pig. Furthermore, it is suggested that the pig is a suitable model for studies of allergic reactions in the airways, if metyrapone is used to keep plasma cortisol levels within a normal range.