A dose-response relationship between exposure to cockroach allergens and induction of sensitization in an experimental asthma in Hartley guinea pigs

Objective: An indoor allergen, cockroach allergen (CRa) has been partly implicated in the rising prevalence of inner-city asthma. This study investigates a dose-response relationship of exposure to CRa with the degree of sensitization and with airway inflammation through the use of our established guinea pig asthma model. Methods: Four groups of Hartley guinea pigs were exposed to aerosolized saline (control) and three dose levels of CRa: low-dose, 0.5 mg (LD); medium-dose, 5 mg (MD); or high dose, 25 mg (HD), nebulized twice a day, 5 days per week, for 4 weeks. The development of anaphylactic antibodies was measured by both allergy skin test and passive cutaneous anaphylaxis assay. Animals were challenged with CRa 5 days after the last sensitization, and specific airway resistance was measured continuously by a double-chamber plethysmograph while animals were in the conscious state. The inflammatory cells in bronchoalveolar lavage fluid (BALF) and the contractile responses of tracheal rings were analyzed in vitro at 24 hours after CRa challenge. Results: The anaphylactic antibodies to CRa were detected in the CRa-sensitized animals by allergy skin test. Passive cutaneous anaphylaxis titers of IgG(1a)-like antibody were zero in control, 1:2 in LD, 1:40 in MD, and 1:160 in HD. Total leukocytes in BALF were increased by CRa challenge in all three CRa-sensitized groups compared with control (p < 0.0001). The tracheal ring from CRa-sensitized guinea pigs constricted upon addition of incremental doses of CRa challenge in vitro in a dose-responsive manner (p < 0.0001). The leukocytosis in BALF and the anaphylactic contractile responses of the tracheal rings in CRa-sensitized groups were correlated to the levels of CRa to which the groups had been exposed during sensitization (p < 0.001). CRa-provoked increase in SRaw was noted in all three groups of the CRa-sensitized guinea pigs compared with control (p < 0.01). Yet, among CRa-sensitized groups, a greater increase in specific airway resistance was noted in the LD group but not in the HD CRa group. Conclusions: The development of anaphylactic cockroach sensitivity in guinea pigs was dependent on the levels of CRa exposure during sensitization, and the CRa-sensitized animals showed antigen-specific airway inflammation along with airway smooth muscle contractions. However, the severity of bronchospasm in conscious animals was not in agreement with the degree of CRa sensitivity.