Effect of Nedocromil Sodium on Early and Late Phase Responses to Allergen Challenge in the Guinea-Pig

Abstract

We have developed a model of asthma in conscious guinea-pigs in which inhalation challenge with specific allergen induces both early and late phase reductions in specific airways conductance. Analysis of cells removed from the airways by bronchoalveolar lavage showed the presence of a neutrophilia, which reached a maximum at 17 hours, and an eosinophilia which developed more slowly, still increasing at 72 hours. Nedocromil sodium inhaled before challenge inhibited both the early and late phase responses. In contrast, the beta-adrenoceptor stimulant, salbutamol, inhibited only the early phase. When inhaled 6 hours after challenge, i.e. between the early and late phase responses, the late phase bronchoconstriction was prevented by nedocromil sodium but only partially by salbutamol. Evidence that the neutrophilia was not functionally associated with the late response was gained from the observations that it was inhibited by both nedocromil sodium and salbutamol, whereas only nedocromil sodium blocked the late phase airways response. When administered 6 hours after challenge, nedocromil sodium reduced eosinophil accumulation at 72 hours in parallel with inhibiting a secondary late response at this time. These results demonstrate that nedocromil sodium is able to prevent both early and late phase reductions in airways function in an animal model of allergic asthma. Whereas inhibition of the early response may reflect an effect on mast cell mediator release, the effects of nedocromil sodium on the late response and on eosinophil accumulation are strongly suggestive of an anti-inflammatory effect within the lung.