Oropharyngeal aspiration: an alternative route for challenging in a mouse model of chemical-induced asthma.
BACKGROUND
To assess the importance of the route of challenge in an existing mouse model of chemical-induced asthma, we replaced intranasal instillation by oropharyngeal aspiration. To our knowledge, oropharyngeal aspiration as a challenge route has not yet been investigated in a mouse model of chemical-induced asthma.


METHODS
On days 1 and 8, mice were dermally sensitized with toluene diisocyanate (TDI) (0.3%) [or vehicle (acetone/olive oil)] and on day 15 they received a single challenge, via oropharyngeal aspiration, with TDI (0.01%) or vehicle. One day after challenge, airway reactivity to methacholine was measured by a forced oscillation technique (FlexiVent) and total and differential cell counts, as well as levels of KC, IL-5, IL-17 and TNF-alpha, were assessed in the bronchoalveolar lavage (BAL) fluid. Lymphocytes from the auricular and mediastinal lymph nodes were cultured to determine the concanavaline A-induced secretion of IL-2, IL-4, IL-10, IL-13, IL-17 and IFN-gamma. Total serum IgE was measured.


RESULTS
In TDI-sensitized mice, a significant increase in airway reactivity was found after a single oropharyngeal challenge with TDI. BAL neutrophils and eosinophils were increased 7- and 5-fold, respectively. An upregulation of Th1 (IFN-gamma), Th2 (IL-4, IL-10, IL-13) and Th17 (IL-17) cytokines was found in the auricular lymph nodes, in the mediastinal lymph nodes only IL-4 was upregulated. The total serum IgE level in TDI-sensitized mice was significantly increased when compared to control mice.


CONCLUSIONS
We conclude that challenging mice via oropharyngeal aspiration mimics the characteristics of human asthma well, without the possible drawbacks of other techniques.
Research Unit of Lung Toxicology, Katholieke Universiteit Leuven, Herestraat 49 bus 706, B-3000 Leuven, Belgium.
Vanessa
V
De Vooght
Jeroen A J
JA
Vanoirbeek
Steven
S
Haenen
Erik
E
Verbeken
Benoit
B
Nemery
Peter H M
PH
Hoet
D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016085:Bronchoconstrictor Agents; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D053120:Respiratory Aspiration; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D015854:Up-Regulation / Q000276:immunology
D016085:Bronchoconstrictor Agents; D016207:Cytokines; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E