Pharmacological characterisation of a new model of antigen-induced pulmonary late-phase reaction in the conscious guinea pig which uses additional polymyxin B inhalation

Abstract

The aim of the present study was to develop a new model of allergic late-phase reaction in the airways of concious guinea pigs (GPs) and to characterise it by pharmacological in tervention. GPs were pretreated with cyclophosphamide and sensitized with ovalbumin (OA) in Al(OH)₃. Weeklt inhalations of polymyxin B were performed before and during sensitization and continued throughout the study period. Under cover of 10 mg/kg i.p. mepyramine all GPs still exhibtied a pronounced immediate reaction (IR), peaking during the first 15 min after OA. Nine out of 15 GPs demonstrated, during screening, a reproducible (twice) second phase (late phase reaction (LPR) of decreased airflow and tidal volume (TV) peaking 4–8 h after OA. In a cross over study, methylprednisolone (MP) at 30 mg/kg p.o. (16 h and 1 h before OA) significantly inhibited the LPR at its peak (4–8 h) peak decrease of TV to % of basal; control 49.4 ± 3.7; MP 78.9 ± p < 0.01; n = 7). After another booster sensitization with 2 μg OA/GP under the same conditions, the Paf-antagonist WEB 2347 at 3 mg/kg p.o. (1 h before OA) inhibited the LPR at its peak agin (peak decrease of TV to % of basal: control 57.3 ± 3.5; WEB 2347 74.8 ± 7.6; p < 0.01; n = 6). In conclusion more than 50% of repeatedly ovalbumin sensitized (and polymyxin B-treated) unanaesthetized GPs developed a reproducible pulmonary late phase reaction (LPR). The LPR peaked at 4–8 h after antigen-exposure. The inhibitory effect by a glucocorticoid and the Paf-antagonist WEB 2347 suggests the inflammatory nature of the LPR and the involvement of platelet-activating factor (Paf) in this model.