Antagonism of antigen-induced contraction of guinea pig and human airways

Abstract

EXPOSURE of isolated sensitised guinea pig or human airway tissue to specific antigen produces a rapid and prolonged contraction which has been studied as a model of asthmatic bronchospasm. This response is thought to be mediated by endogenous chemicals released from airway mast cells, since antigen treatment of sensitised guinea pig or human pulmonary tissue results in the elaboration of several substances, including histamine and slow reacting substance of anaphylaxis (SRS-A), which can contract airway smooth muscle. The few attempts at investigation of which mediators are responsible for the airways response have led to contradictory conclusions. Schild et al.¹ reported that antihistamines significantly (but not completely) antagonised antigen-induced contraction of bronchi from an asthmatic patient. Sheard and Blair², however, demonstrated that antihistamines had no effect on the contraction of human bronchial strips studied in the presence of antigen-challenged, passively-sensitised human lung. They suggested, without direct evidence, that the contractile response of the bronchial strip was the result of SRS-A release. At present, therefore, the roles of histamine and SRS-A in the airway response to antigen have not been defined. We have investigated the effects of diphenihydramine, a histamine H₁ antagonist, and FPL 55712 (ref. 3), an SRS-A antagonist, on the response of sensitised guinea pig and human airways to antigen and report that pretreatment with either alone modifies the airway response in a characteristic fashion, and that together, they effectively inhibit antigen-induced airway constriction.