Using a newly developed guinea-pig model of asthma, characterized by allergen-induced early and late phase asthmatic reactions, bronchial hyperreactivity (BHR) and airway inflammation, the importance of eosinophil activation for the development of BHR to inhaled histamine was investigated at 6 h (after the early reaction) and 24 h (after the late reaction) after allergen provocation. Eosinophil activation was assessed by a sensitive kinetic assay for eosinophil peroxidase (EPO) activity, suitable for bronchoalveolar lavage (BAL) analysis. A significant 2±9-fold (P < 0±01) increase in bronchial reactivity to histamine was observed 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 allergen exposure the bronchial reactivity to histamine was lower (1±7-fold), but still significantly enhanced (P < 0±01). By contrast, the number of eosinophils was further increased compared with 6 h after provocation (3±8-fold, P < 0±05), while the EPO activity remained stable at 6 h levels. The number of eosinophils was significantly correlated with EPO activity at 6 h (r = 0±62; P < 0±05), but not at 24 h after provocation. No significant correlation was observed between the number of eosinophils in the BAL fluid and BHR to histamine at either time point. Remarkably, EPO activity was significantly correlated to BHR at 24 h (r = 0±66; P < 0±004), but not at 6 h after provocation. These results indicate that: newly infiltrated eosinophils have the highest activation state during the early asthmatic reaction; EPO may play a role in the development of BHR to inhaled histamine after the late reaction and that besides EPO, additional mechanisms may contribute to BHR to histamine after the early asthmatic reaction.
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