A Al ll le er rg ge en n--i in nd du uc ce ed d l la at te e--p ph ha as se e a ai ir rw wa ay ys s o ob bs st tr ru uc ct ti io on n i in n t th he e p pi ig g: : m me ed di ia at to or r r re el le ea as se e a an nd d e eo os si in no op ph hi il l r re ec cr ru ui it tm me en nt t ABSTRACT: The aim of this study was to develop a novel model for studies of mediator mechanisms involved in the late asthmatic reaction in the lower airways, by using the sensitized pig. The release of histamine and cysteinyl-containing leukotrienes (cys-LTs), as well as the levels of inflammatory cells in blood and bronchoalveolar lavage fluid, were determined and their relationship to plasma cortisol levels and pulmonary airways obstruction was noted. Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen, and one group of animals was treated with a cortisol-synthesis inhibitor (metyrapone) by constant intravenous infusion. Ascaris suum allergen was nebulized into the lower airways and total lung resistance, blood leucocyte count and urinary levels of methylhistamine and leukotriene E 4 (LTE 4 ) were followed for 8 h, whereafter bronchoalveolar lavage was performed for analysis of leucocytes.An increase in urinary methylhistamine and LTE 4 was seen during the acute allergic reaction in both groups of pigs. Metyrapone treatment prolonged the acute release of histamine, and this was seen together with a prolonged acute bronchoconstrictor response. In metyrapone-treated pigs, a continuous release over 8 h was seen for cys-LTs, but not for histamine. A late blood eosinophilia was also seen in metyrapone-treated animals, starting 4-6 h after allergen challenge. Late cys-LT release and eosinophilia were absent in non-metyrapone-treated animals.These results suggest that allergen-induced late release of cys-LTs as well as blood eosinophilia occur simultaneously with late-phase airways obstruction in the pig, and that all these reactions are prevented by high levels of endogenous cortisol. Eur Respir J., 1995Respir J., , 8, 1100Respir J., -1109 The association between increased numbers of eosinophils in the lung and human bronchial asthma was shown by ELLIS [1] in 1908, and is today well-established. However, the exact mechanism of action of eosinophils and the relevance of the eosinophilia sometimes seen in asthma are not yet fully understood. We wanted to establish a large animal model for studies of the initiation of allergic inflammation in the airways, and the pig has been found to be suitable for such studies [2][3][4].The mast cell plays a pivotal role in the acute asthmatic response, in that it releases mediators, such as histamine and cysteinyl-containing leukotrienes (cys-LTs) [5]. Measurements of free levels of histamine and cysLTs in plasma may be difficult, due to uncontrolled release from blood leucocytes. Therefore, the relatively stable urinary end-metabolites methylhistamine [6] and leukotriene E 4 (LTE 4 ) [7], respectively, were measured in this study. The possible involvement of cys-LTs in t...