Site-specific sensitization in a murine model of allergic rhinitis: role of the upper airway in lower airways disease.
BACKGROUND
Allergic rhinitis (AR) is the most common atopic disease with strong links to asthma. We have developed a murine model of AR to study nasal, bronchial, and systemic immune response to local allergen stimulation.


OBJECTIVE
The purpose of this study was to develop and characterize a murine model of AR.


METHODS
Six- to 8-week-old BALB/c mice were sensitized by means of intranasal (local) application of ovalbumin (OVA) or systemic intraperitoneal injection. They were then challenged with intranasal OVA, and allergic response was assessed.


RESULTS
Intranasal particle deposition was found to be exclusively in the nares. All sensitized animals showed increased levels of OVA-specific serum IgE and IgG after challenge, although the timing to maximal response varied with the route and dose of allergen used. Histology of the upper and lower airways showed marked eosinophilic infiltration, and analysis of bronchoalveolar lavage fluid showed increased IL-5 and PMN infiltrates after challenge.


CONCLUSIONS
Using exclusive local sensitization and challenge of mouse nares, we were able to demonstrate inflammatory changes in both the upper and lower airways, even though distribution of allergen particles appeared to be only in the nares of these animals. This provides further evidence for the importance of the upper airway in lower airways disease. We have shown that the route of administration greatly affects the characteristics of the subsequent immune responses.
McCusker
Christine
C
Division of Allergy and Immunology, Montreal Children's Hospital Research Institute and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Chicoine
Martin
M
Hamid
Qutayba
Q
Mazer
Bruce
B
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000473:pathology*
D007074:Immunoglobulin G; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin