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 bi?en part ly implicated in the rising prevalence of inner-city asthma. This stud y investigates a dose-response relationship of exposure to CRa with th e degree of sensitization and with airway inflammation through the use of our established guinea pig asthma model. Methods: Four groups of H artley guinea pigs were exposed to aerosolized saline (control) and th ree 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 b oth allergy skin test and passive cutaneous anaphylaxis assay. Animals were challenged with CRa 5 days after the last sensitization, and spe cific airway resistance was measured continuously by a double-chamber plethysmograph while animals were in the conscious state. The inflamma tory cells in bronchoalveolar lavage fluid (BALF) and the contractile responses of tracheal rings were analyzed in vitro at 24 hours after C Ra challenge. Results: The anaphylactic antibodies to CRa were detecte d in the CRa-sensitized animals by allergy skin test. Passive cutaneou s anaphylaxis titers of IgG(ln)-like antibody were zero in control, 1: 2 in LD, 1:40 in MD, and 1:160 in HD. Total leukocytes in BALF were in creased by CRa challenge in all three CRa-sensitized groups compared w ith control (p < 0.0001). The tracheal rings from CRa-sensitized guine a pigs constricted upon addition of incremental doses of CRa challenge in vitro in a dose-responsive manner (p < 0.0001): The leukocytosis i n BALF and the anaphylactic contractile responses of the tracheal ring s in CRa-sensitized groups were correlated to the levels of CRa to whi ch the groups had been exposed during sensitization (p < 0.001). CRa-p rovoked increase in SRaw was noted in all three groups of the CRa-sens itized guinea pigs compared with control (p < 0.01). Yet, among CRa-se nsitized groups, a greater increase in specific airway resistance was noted in the LD group but not in the HD CRa group. Conclusions: The de velopment of anaphylactic cockroach sensitivity in guinea pigs was dep endent 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 bronc hospasm in conscious animals,vas not in agreement with the degree of C Ra sensitivity.