Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment

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 E4 (LTE4) were followed for 8 h, whereafter bronchoalveolar lavage was performed for analysis of leucocytes. An increase in urinary methylhistamine and LTE4 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.

This article has been cited by other articles:

				F. Petak, W. Habre, B. Babik, J. Tolnai, and Z. Hantos Crackle-sound recording to monitor airway closure and recruitment in ventilated pigs. Eur. Respir. J., April 1, 2006; 27(4): 808 - 816. [Abstract] [Full Text] [PDF]

				P. B. Noble, D. J. Turner, and H. W. Mitchell Relationship of airway narrowing, compliance, and cartilage in isolated bronchial segments J Appl Physiol, March 1, 2002; 92(3): 1119 - 1124. [Abstract] [Full Text] [PDF]

				D.J. Turner, P.R. Gray, S.A. Taylor, J. Thomas, and H.W. Mitchell Physiological responses of the airway wall and lung in hyperresponsive pigs Eur. Respir. J., December 1, 2001; 18(6): 935 - 941. [Abstract] [Full Text] [PDF]

				R. C. O. Zanardo, E. Costa, H. H. A. Ferreira, E. Antunes, A. R. Martins, F. Murad, and G. De Nucci Pharmacological and immunohistochemical evidence for a functional nitric oxide synthase system in rat peritoneal eosinophils PNAS, December 9, 1997; 94(25): 14111 - 14114. [Abstract] [Full Text] [PDF]