web-2347 and Disease-Models--Animal

The aim of the present study was to develop a new model of allergic late-phase reaction in the airways of conscious guinea pigs (GPs) and to characterise it by pharmacological intervention. GPs were pretreated with cyclophosphamide and sensitized with ovalbumin (OA) in Al(OH)3. Weekly 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 exhibited 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 +/- 7.5; p < 0.01: n = 7). After another booster sensitization with 2 micrograms 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 again (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.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Antigens; Asthma; Azepines; Disease Models, Animal; Guinea Pigs; Histamine H1 Antagonists; Hypersensitivity, Delayed; Male; Ovalbumin; Polymyxin B; Pyrilamine; Triazoles