THE IMPORTANCE OF EOSINOPHIL ACTIVATION FOR THE DEVELOPMENT OF ALLERGEN-INDUCED BRONCHIAL HYPERREACTIVITY IN CONSCIOUS, UNRESTRAINED GUINEA-PIGS

Using a newly developed guinea-pig model of asthma, characterized by a llergen-induced early and late phase asthmatic reactions, bronchial hy perreactivity (BHR) and airway inflammation, the importance of eosinop hil activation for the development of BHR to inhaled histamine was inv estigated at 6 h (after the early reaction) and 24 h (after the late r eaction) after allergen provocation. Eosinophil activation was assesse d by a sensitive kinetic assay for eosinophil peroxidase (EPO) activit y, suitable for bronchoalveolar lavage (BAL) analysis. A significant 2 .9-fold (P < 0.01) increase in bronchial reactivity to histamine was o bserved at 6 h after allergen exposure, which was associated with a 2. 9-fold increase in the number of eosinophils (P < 0.05) and a 6.7-fold increase in EPO activity (P < 0.01) in the BAL fluid. At 24 h after a llergen exposure the bronchial reactivity to histamine was lower (1.7- fold), but still significantly enhanced (P < 0.01). By contrast, the n umber of eosinophils was further increased compared with 6h after prov ocation (3.8-fold, P < 0.05), while the EPO activity remained stable a t 6h levels. The number of eosinophils was significantly correlated wi th EPO activity at 6 h (r = 0.62; P < 0.05), but not at 24 h after pro vocation. No significant correlation was observed between the number o f eosinophils in the BAL fluid and BHR to histamine at either time poi nt. Remarkably, EPO activity was significantly correlated to BHR at 24 h (r = 0.66; P < 0.004), but not at 6h after provocation. These result s indicate that: newly infiltrated eosinophils have the highest activa tion state during the early asthmatic reaction; EPO may play a role in the development of BHR to inhaled histamine after the late reaction a nd that besides EPO, additional mechanisms may contribute to BHR to hi stamine after the early asthmatic reaction.