Interleukin-13-dependent bronchial hyper-responsiveness following isolated upper-airway allergen challenge in a murine model of allergic rhinitis and asthma.
BACKGROUND
We have previously shown that isolated allergic sensitization and challenge of the upper airway results in lower-airway inflammation, which supports the concept of the united airways.


OBJECTIVE
This study investigates the hypothesis that isolated upper-airway allergic sensitization is sufficient to induce bronchial hyper-responsiveness (BHR), characteristic of asthma, and that IL-13 is an essential mediator in both the upper and lower airways.


METHODS
BALB/c mice were sensitized and challenged by intranasal instillation of allergen ovalbumin (OVA) using our standard protocol. BHR to methacholine was determined and inflammation in nares and lung was assessed.


RESULTS
Isolated intranasal application of allergen in awake animals resulted in almost exclusive deposition in the upper airways while in anaesthetized mice there was almost equal distribution in the upper and lower airways. We have demonstrated significant BHR to methacholine challenge in animals receiving OVA only in the upper airway. Also noted was concomitant increase in eosinophilic infiltrates in lung and nares as well as increased granulocytes and IL-13 levels in bronchoalveolar lavage (BAL) fluid. Using a polyclonal anti-IL-13 antibody we have shown inhibition of airways inflammation, both in nares and in lung with significant reduction of granulocytes in BAL from anti-IL-13 treated mice (P<0.0001). Anti-IL-13 treatment also abrogates allergen-induced BHR (P<0.01).


CONCLUSIONS
These data suggest that isolated upper-airway allergen deposition initiates allergic responses along the entire airway. IL-13 mediates both airway inflammation and BHR and may play a role in the communication between the upper and lower airways.
Wang
Y
Y
Montreal Children's Hospital Research Institute, Montreal, Canada.
McCusker
C T
CT
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D001980:Bronchi / Q000276:immunology*; D001985:Bronchial Provocation Tests / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000276:immunology*; D016210:Methacholine Chloride / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*
D000485:Allergens; D007074:Immunoglobulin G; D018793:Interleukin-13; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin