title: Airway responsiveness in an allergic rabbit model.
abstract: BACKGROUND
  Animal models of allergy and bronchial hyperresponsiveness (BHR) are useful in researching pulmonary diseases and evaluating drug effects on the airways. Neonatally immunised rabbits exhibit several features of asthma as adults, including early and late airway responses following antigen challenge, oedema and inflammatory cell infiltration into the lung, BHR to inhaled histamine and methacholine (compared with naïve rabbits) and exacerbations of BHR following antigen challenge. Therefore this model can be used to investigate the underlying mechanisms of BHR and for the preclinical evaluation of new drugs for the treatment of asthma.
  
  
  OBJECTIVE
  To describe the characteristics of airway responses in a rabbit model of allergic inflammation and to evaluate the relationship between skin test reactivity to antigen, airway inflammation and BHR.
  
  
  METHODS
  New Zealand White rabbits were neonatally immunised against Alternaria tenius. At 3 months of age, airway responsiveness was measured to aerosolised histamine, methacholine or allergen. Bronchoalveolar lavage (BAL) was performed and cell counts recorded. Direct skin tests were performed to assess skin reactivity to allergen and passive cutaneous anaphylaxis (PCA) tests were performed to determine titres of circulating IgE.
  
  
  RESULTS
  In a population of allergic rabbits, allergen challenge induced a significant bronchoconstriction, airway inflammation and BHR. Skin test responsiveness to allergen did not correlate with various indices of pulmonary mechanics e.g. baseline sensitivity to methacholine and histamine, or allergen-induced BHR. In contrast, skin test responsiveness did predict airway inflammation as assessed by measurements of eosinophil recruitment to the lung.
  
  
  CONCLUSIONS
  The allergic rabbit is a useful model to further our understanding of allergic diseases. Recording lung function using a minimally invasive procedure allows repeated measurements to be made in rabbits longitudinally, and each animal may thus be used as its own control. Our observations do not support the use of skin responsiveness to allergen as a predictor of airway sensitivity as we observed no correlation between skin sensitivity and airway responsiveness to inhaled histamine, methacholine or allergen. However, skin reactivity did predict airway inflammation as assessed by measurements of eosinophil recruitment to the lung. Our results also further highlight the likely dissociation between airway inflammation and BHR.
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, 5th Floor Franklin Wilkins Building, Waterloo Campus, London, SE1 9NH, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Keir
authors.forename: D
authors.initials: D
authors.lastname: Spina
authors.forename: G
authors.initials: G
authors.lastname: Douglas
authors.forename: C
authors.initials: C
authors.lastname: Herd
authors.forename: C P
authors.initials: CP
authors.lastname: Page
mesh_terms: D000485:Allergens / Q000276:immunology; D000528:Alternaria / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D016084:Bronchoconstriction / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D006632:Histamine / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride / Q000276:immunology; D011817:Rabbits; D012129:Respiratory Function Tests; D012882:Skin Tests / Q000379:methods
chemical_list: D000485:Allergens; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D006632:Histamine