ToxSci Advance Access originally published online on February 18, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences 72, 113-121 (2003)
Copyright © 2003 by the Society of Toxicology
IMMUNOTOXICOLOGY |
Systemic Administration of Bordetella pertussis Enhances Pulmonary Sensitization to House Dust Mite in Juvenile Rats
Immunotoxicology Branch, MD-92, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina
The incidence of allergies and asthma has increased significantly in the past few decades. The objectives of this study were to establish an allergy model in weanling rats to more closely reflect the developing immune system of children, and to determine whether systemic administration of inactivated Bordetella pertussis could enhance pulmonary and systemic immune responses to locally administered house dust mite antigen (HDM). Three-week old female Brown Norway rats were sensitized with 10 µg HDM intratracheally or intraperitoneally, with or without a simultaneous injection of 108 whole killed B. pertussis organisms. Ten days later, all the rats were challenged with 5 µg HDM via the trachea. Bronchial lymph nodes and bronchoalveolar lavage fluid (BAL) were collected 0, 2, and 4 days post-challenge. Coadministration of pertussis and intratracheal instillation of HDM enhanced HDM-specific lymphoproliferative responses and increased BAL levels of total protein, lactate dehydrogenase, HDM-specific IgE and IgG antibodies, and the number of eosinophils in BAL to the same extent as had occurred in the systemically immunized animals. The data show that intratracheal instillation of HDM induces a mild allergic sensitization in juvenile rats, and that ip injection with B. pertussis enhances this sensitization process to levels seen in animals injected with antigen and B pertussis together. These results suggest that simultaneous exposure to Th2-inducing vaccine components and allergenic proteins may be a risk factor for allergic sensitization and the development of asthma in susceptible individuals.
Key Words: pertussis; dust mite; allergy; IgE; lymphocyte; eosinophil; vaccine; rat.