Characteristics of weekly pulmonary hypersensitivity responses elicited in the guinea pig by inhalation of ovalbumin aerosols

Abstract

We have reported the development of a guinea pig animal model for pulmonary hypersensitivity to inhaled chemicals in which respirations of animals are monitored continuously for 24 hr permitting detection of immediate- (IAR) and late-onset (LAR) airway reactions. Additionally implanted temperature transmitters allow determination of accompanying febrile responses. The current study investigated the relationship between severity of IAR and occurrence of LAR in individual animals. To quantify severity, a grading system was devised which took into account time to response, increase in breathing rate, and occurrence of airway constriction (ACR). Guinea pigs were sensitized by ip injection with 1 mg ovalbumin (OA). On Day 14, inhalation challenge with 12 mg/m 3 OA resulted in severe IAR in all animals. No LAR were detected. Subsequent weekly inhalation challenges with OA resulted in less severe IARs and occasionally in absence of response. Febrile reactions were not detected. On one occasion a LAR was observed. It occurred in the animal demonstrating the most severe IARs and having the highest titer of specific homocytotropic antibody. These results are consistent with the mechanism of IAR involving release of spasmogenic mediators from mast cells as a result of antigen crosslinking of surface antibody. The mechanism of the LAR is addressed in the accompanying paper in which LARs are more consistently produced in OA-sensitized guinea pigs.