Antigen-induced Acute and Late-phase Responses in Primates

We have examined the proinflammatory cell influx as well as the levels of eosinophil and neutrophil-derived granule proteins in BAL fluid obtained from monkeys undergoing acute and late-phase (dual) or single acute bronchoconstriction following antigen inhalation. Prior to antigen inhalation, there was a significantly higher number (and percentage) of eosinophils in BAL fluid from dual responder monkeys as compared with single responders. The late-phase response (LPR) (6 to 8 h postantigen) was associated with a decrease in the number of BAL eosinophils and an increase in the levels of BAL fluid EPO that returned to baseline levels by 24 h postantigen inhalation. In contrast, the number of BAL neutrophils prior to antigen inhalation were low. Concurrent with the LPR, the number of BAL neutrophils and the concentration of EPO in BAL fluid were significantly increased above that occurring in single responders. Chronic treatment (7 days) with dexamethasone significantly reduced the number of BAL eosinophils and the BAL levels of EPO prior to antigen inhalation in dual responder (LPR) monkeys and significantly blocked the dual response and both the associated neutrophil influx into the airways and an increase in BAL fluid EPO during the LPR. We conclude that, in this primate model, eosinophil activation and a large influx of neutrophils into the airways is associated with the occurrence of the antigen-induced late-phase airway obstructive response.