ALLERGEN-INDUCED LATE-PHASE AIRWAYS OBSTRUCTION IN THE PIG - THE ROLEOF ENDOGENOUS CORTISOL

In developing a novel model for studies of the allergen-induced late-p hase airways obstruction, by using the pig, the importance of endogeno us cortisol levels was examined by the use of metyrapone, a cortisol-s ynthesis inhibitor. Specific-pathogen free pigs were actively sensitiz ed with Ascaris suum allergen, One group of pigs was treated with a co nstant infusion of metyrapone in order to maintain low levels of plasm a cortisol Ascaris suum allergen was nebulized into the lower airways and plasma cortisol and catecholamine levels, total lung resistance an d dynamic compliance, blood gases and pH, and blood now in the bronchi al circulation were continuously recorded for 8 h. At the time of alle rgen challenge, the plasma cortisol levels in sensitized pigs were 455 +/-37 nM and 40.1+/-3.8 nM in non-metyrapone-treated and metyrapone-tr eated pigs, respectively, No difference was seen between the magnitude of the acute bronchoconstrictor response in the two groups, A late ai rways obstruction, starting at about 4 h, developed only in pigs with low cortisol levels, whereas a late increase in blood flow in the bron chial circulation was seen in both groups, even if a late airways obst ruction was absent. Plasma adrenaline did not seem to influence the la te-phase reaction. These results suggest that endogenous cortisol leve ls, but not adrenaline, modify the late response to allergen in the pi g, Furthermore, it is suggested that the pig is a suitable model for s tudies of allergic reactions in the airways, if metyrapone is used to keep plasma cortisol levels within a normal range.