The role of slow-reacting substance of anaphylaxis in the late bronchial response after antigen challenge in allergic sheep.

Allergic sheep respond to inhalation challenge with Ascaris suum antigen with an immediate bronchoconstriction that resolves within 2 to 4 h, followed by a second bronchial obstruction occurring 6.5 to 8 h after challenge. The purpose of this study was to determine if the antigen-induced late bronchial response in allergic sheep is mediator dependent and to determine the extent to which histamine and/or slow-reacting substance of anaphylaxis (SRS-A) are involved in this response. To do this, 10 conscious sheep with Ascaris suum hypersensitivity underwent an inhalation challenge with antigen, and the average increase in specific lung resistance (SRL = mean pulmonary flow resistance times thoracic gas volume) was determined for each animal between 6.5 and 8 h after challenge, i.e., the time of late bronchial response. On another occasion, separated by at least 14 days, the animals were rechallenged with antigen, but prior to the onset of the late response (5.5 h) the animals were treated with either the mast cell stabilizer cromolyn (1 mg/kg), the SRS-A antagonist FPL-55712 (3 ml of a 1% wt/vol solution), or the histamine H1. receptor antagonist chlorpheniramine (2 mg/kg). Compared with the control response, inhaled aerosols of cromolyn or FPL-55712 blocked the late increase in SRL (p less than 0.01). Intravenously administered chlorpheniramine alone, or in conjunction with atropine, had no effect on the late response. Finally, the late response was partially reversed by FPL-55712 inhalation. These results suggest that the late bronchial response after inhalation challenge in allergic sheep is mediator dependent, and that SRS-A is a principal mediator of this response.