Intratracheal Sensitization/Challenge-Induced Biphasic Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

In most experimental model of asthma using guinea pigs, the animals are made to inhale an aerosolized antigen which passes through the nasal cavity In the present study, we attempted to create an animal model of asthma showing a biphasic asthmatic response and airway hyperresponsiveness, in which the allergic responses are restricted to the lung Guinea pigs were sensitized by the intratracheal instillation of ovalbumin (OVA)+Al(OH)(3) once a day for 7d, and then intratracheally challenged with OVA 12d after the last sensitization The change in specific airway resistance (sRaw) and airway responsiveness to histamine were measured Pranlukast (100 mg/kg), theophylline (50 mg/kg), and dexamethasone (10 mg/kg) were orally administered 18 and 2h before the antigen challenge The challenge caused a marked biphasic elevation of sRaw with peaks at 5 min and 4h At 24h, airway hyperresponsiveness to histamine was observed Pranlukast, theophylline, and dexamethasone suppressed the late asthmatic response and airway hyperresponsiveness The early asthmatic response was inhibited by theophylline and dexamethasone In conclusion, the intratracheal sensitization and challange caused a biphasic asthmatic response and airway hyperresponsiveness in guinea pigs This model may be useful for the evaluation of anti-asthma drugs