The Effect of Cromolyn Sodium and Albuterol on Early and Late Phase Bronchoconstriction and Airway Leukocyte Infiltration after Allergen Challenge of Nonanesthetized Guinea Pigs

Publisher Website
Google Scholar
Abstract
We describe the effects of the antiallergic drug cromolyn sodium and the β2-selective adrenoceptor agonist albuterol against early and late phase changes in specific airways conductance (sGaw) and leukocyte infiltration into the airways after allergen challenge of nonanesthetized guinea pigs. Inhalation of ovalbumin by sensitized guinea pigs induced three phases of airways obstruction: an early asthmatic response (EAR) peaking at 2 h, a late response (LAR) peaking at 17 h, and a further late response (LLAR) being observed at 72 h. The LAR was accompanied by a 13-fold rise in neutrophils and a four-fold rise in eosinophils recovered by bronchoalveolar lavage (BAL) at 17 h. By 72 h, the BAL content of neutrophils had returned to near normal, whereas eosinophil numbers had risen to 6.7-fold above baseline. Inhalation of an aerosolized solution of cromolyn, 10 mg/ml, 15 min before challenge inhibited both the EAR and LAR and the influx of neutrophils into the airways at 17 h but had no effect on eosinophil accumulation. Inhalation of cromolyn at 6 h, i.e., after the completion of the EAR, inhibited the LAR, the LLAR, and the rise in eosinophils at 72 h but did not reduce the influx of neutrophils at 17 h. Administration of cromolyn at both 15 min before and 6 h after challenge inhibited all changes in sGaw and reduced the accumulation of neutrophils at 17 h and the influx of eosinophils at 72 h. In contrast, inhalation of albuterol, 0.1 mg/ml, 15 min before allergen provocation blocked the EAR and the rise in BAL neutrophils at 17 h but did not inhibit the LAR. Inhalation of albuterol at 6 h partially reversed the LAR but had no effect on either the LLAR or cellular changes. Given at both times, albuterol inhibited the EAR and neutrophil accumulation at 17 h and partially reversed the LAR but produced no other effects. The comparative effects of cromolyn and albuterol on the EAR, the LAR, and neutrophil accumulation strongly suggests influx of this cell into the airways occurs as a direct consequence of mediator release during the EAR and that, although there is a temporal relationship between neutrophil accumulation and the LAR, these events are not functionally related in the guinea pig. Furthermore, the ability of cromolyn administered at 6 h after challenge to inhibit the LAR, the LLAR, and eosinophil accumulation at 72 h strongly suggest that these events are initiated subsequent to the completion of the EAR. The similarities between the effects of inhibitory drugs in this guinea pig model and their clinical activity suggest that this is a valid animal model of allergen-induced asthma that will allow us to perform studies of an invasive nature which would not be possible in humans.

This publication has 29 references indexed in Scilit: