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

This study was presented partly at AAAI/AAI/CIS joint meeting in San Francisco, Calif., February 21 to 26, 1997.
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Abstract

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 IgG1a-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 rings 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.(J Allergy Clin Immunol 1998;101:653-9.)

Section snippets

Animals

Male Hartley strain guinea pigs weighing 200 to 250 gm were purchased from Hilltop Laboratories (Scotsdale, Pa.). Upon arrival, two animals were housed in a plastic cage in a colony room with a 12-hour day-night cycle (lights on at 7 am) through artificial illumination. They received food and water ad libitum. Before the start of the experiment, guinea pigs were quarantined and acclimatized to their housing for 1 week. The experiment was carried out with the approval of the Institutional Animal

Anaphylactic sensitization

As shown in Table I, the saline-sensitized guinea pigs (control) showed negative reactions to the CRa skin test, whereas in the CRa-sensitized guinea pigs, LD, MD, or HD revealed positive reactions (p < 0.001).

. Results of CRa skin test

GroupSalineCRa 0.5 μgCRa 1 μgCRa 5 μgHistamine
Control (n = 11)0.0 ± 0.00.0 ± 0.00.0 ± 0.00.3 ± 0.212.3 ± 0.4
LD (n = 6)0.0 ± 0.07.6 ± 0.39.2 ± 0.712.5 ± 0.314.3 ± 0.3
MD (n = 6)0.0 ± 0.07.5 ± 0.610.0 ± 0.612.4 ± 0.612.8 ± 0.3
HD (n = 6)0.0 ± 0.07.4 ± 0.211.0 ± 0.2

Discussion

This study further demonstrates that aerosolized CRa exposure alone sensitizes animals to CRa and that the sensitized animals develop an antigen-specific “asthma-like” airway obstruction on CRa inhalation. This confirms previous studies from this laboratory.14, 15 Moreover, the anaphylactic sensitization appears to be correlated to the levels of CRa exposures of the guinea pigs during the sensitization period (Fig. 1 and Table II, Table III). However, the airway obstruction as manifested by the

Acknowledgements

We thank Mrs. Betsy Dennis for word processing assistance, James E. Burgett for editorial assistance, and Dr. Mary K. Rayens for assistance in data statistical analysis.

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    From athe Division of Allergy and Immunology, the Department of Internal Medicine, and bthe Department of Physiology, University of Kentucky, Lexington.

    ☆☆

    Supported by the Center for Indoor Air Research.

    Reprint requests: Daohong Zhou, MD, Division of Allergy and Immunology, Department of Internal Medicine, University of Kentucky, 800 Rose St., Lexington, KY 40536.

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