Effect of Nedocromil Sodium on Antigen-Induced Airway Responses in Allergic Sheep

Abstract

We studied the effects of nedocromil sodium and sodium cromoglycate on early and late bronchial responses, the airway inflammation associated with the late response to inhaled Ascaris suum antigen in allergic sheep in vivo, and the antigen-induced contractile responses of sheep tracheal smooth muscle in vitro. In addition, we examined the effect of nedocromil sodium on the development of antigen-induced airway hyper-responsiveness in this model. Pretreatment with either nedocromil sodium or sodium cromoglycate was effective in blocking antigen-induced early and late responses in allergic sheep. Both drugs also prevented the influx of eosinophils into the airways as assessed by bronchoalveolar lavage, observed during the late response in this model. No difference in drug potency was observed in vivo, but in vitro nedocromil sodium was 10-fold more potent than sodium cromoglycate against antigen-induced contractions of sheep tracheal smooth muscle. Nedocromil sodium was effective in blocking antigen-induced late responses and the subsequent development of airway hyper-responsiveness irrespective of whether the drug was given before antigen challenge or after the immediate response to antigen but before the late response. These findings indicate that nedocromil sodium is effective in the sheep model of asthma and therefore may be beneficial in the treatment of reversible obstructive airway disease in man.