NEDOCROMIL SODIUM BLOCKS THE EARLY AND LATE PHASES OF ALLERGEN CHALLENGE IN A GUINEA-PIG MODEL OF ASTHMA

We developed a model of asthma in conscious guinea pigs in which both early- and late-phase reductions in specific airways conductance are demonstrable after inhalation challenge. Neutrophilia that peaks 17 hours after challenge was discovered by bronchoalveolar lavage in this model, as was eosinophilia that develops more slowly, peaking at 72 hours. Nedocromil sodium blocked both the early- and late-phase reductions in airflow, but salbutamol blocked only the early phase. Both drugs blocked the neutrophilia when given before challenge, but not when given 6 hours afterward. This suggests that the neutrophilia is secondary to an intact early phase response. Nedocromil sodium, given 6 hours after challenge, reduced the eosinophilia at 72 hours but not at 17 hours. Salbutamol had no effect on the eosinophilia at either time. These results suggest that nedocromil sodium has antiinflammatory properties in the lung that are not shared by the beta2-adrenergic stimulant drug, salbutamol.