Repeated antigenic challenge-induced airway hyperresponsiveness and airway inflammation in actively sensitized rats

Airway hyperresponsiveness (AHR) is a critical component in bronchial asthma, but the underlying mechanisms remain to be disclosed. Our present studies were performed to establish a new good experimental animal model of AHR. Male Wistar rats actively sensitized with DNP-Ascaris antigen (DNP-Asc) were challenged by inhaling DNP-Asc 8 days after the first immunization (single antigenic challenge). Another sensitization group received 3 challenges every 48 hr (repeated antigenic challenge). The airway responsiveness to inhalations of acetylcholine (ACh) and neurokinin A (NKA) were determined under anesthesia. The airway microvascular leakage was also determined with Evans blue (E.B.). At 24 hr after the single antigen challenge, the airway responsiveness to ACh and NKA were slightly enhanced, and the E.B. exudation was increased in the main bronchus. In contrast, the airway responsiveness to ACh and NKA and the E.B. exudation in the main bronchus were much more markedly enhanced 24 hr after the repeated antigenic challenge. The isolated main bronchial strip from the challenged rats had obtained AHR towards ACh and serotonin. These findings suggest that repeated antigenic challenge causes a distinct AHR, both in vivo and in vitro, and that the airway inflammation may be closely related to pathogenesis of AHR.