Optimisation of the sensitisation conditions for an ovalbumin challenge model of asthma.
Antigen inhalation in patients with atopic asthma results in an early asthmatic response (EAR), accompanied by a late asthmatic response (LAR) in 60% of patients, airway hyperresponsiveness (AHR) and inflammatory cell infiltration to the lungs. An ideal animal model of asthma should, therefore, provide at least these 4 features consistently and reproducibly. The aim of this study was to optimise the ovalbumin (OA) sensitisation conditions, for achieving EAR, LAR, AHR and cell influx, in a guinea-pig model of asthma. Animals were sensitised with 10 micro g or 100 micro g OA, as either a single or booster (day 1 and day 5) injection. Airway responses to inhaled OA (10 micro g, 1 h) of actively sensitised, conscious guinea pigs were determined by whole body plethysmography as the change in specific airways conductance (sG(aw)) over a 12 h period and at 24 h. Bronchoconstriction by inhaled histamine (1 mM) was used to investigate AHR, and inflammatory cell influx was determined by bronchoalveolar lavage (BAL), both at 24 h post-challenge. A single sensitisation with 10 micro g OA did not reveal an EAR, LAR or AHR following exposure to OA. However, total and differential cell counts (eosinophils and macrophages) were significantly greater 24 h post-challenge, when compared to saline-challenged sensitised animals. The addition of a booster injection of 10 micro g revealed an EAR, but no LAR or AHR after ovalbumin inhalation. However, there was a significant cell influx. Sensitisation with 100 micro g OA (single and booster injections) revealed all four parameters of the asthmatic response (EAR, LAR, AHR and cell influx). The incorporation of the booster sensitisation injection resulted in a prolongation of the LAR, and the AHR was more pronounced and cell influx increased significantly, when compared to all other sensitisation protocols. Thus, sensitisation with 100 micro g OA (with a booster injection) can reveal an EAR, LAR, AHR and cell influx following inhalation exposure to OA (10 micro g). Cellular infiltration to the lung may be a poor marker of the asthmatic response, as a threshold level of cell influx (eosinophils) appears to be required in order to elicit the LAR and AHR. There was an association between the LAR and AHR.
Smith
Nicola
N
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff, UK.
Broadley
Kenneth J
KJ
D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007114:Immunization / Q000379:methods*; D008264:Macrophages / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage*
D000485:Allergens; D006632:Histamine; D010047:Ovalbumin