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 μg or 100 μg OA, as either a single or booster (day 1 and day 5) injection. Airway responses to inhaled OA (10 μg, 1 h) of actively sensitised, conscious guinea pigs were determined by whole body plethysmography as the change in specific airways conductance (sGaw) 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 μg 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 μg revealed an EAR, but no LAR or AHR after ovalbumin inhalation. However, there was a significant cell influx. Sensitisation with 100 μg 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 μg OA (with a booster injection) can reveal an EAR, LAR, AHR and cell influx following inhalation exposure to OA (10 μg). 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.