Characterisation of a novel airway late phase model in the sensitized guinea pig which uses silica and Bordetella pertussis as adjuvant for sensitization.
The objective of the present investigation was to validate a novel model of allergic late phase reaction in the airways of conscious guinea pigs by monitoring airway function with CO2-forced respiration. In addition airway inflammation as one possible cause for the development of airway late phase reaction was characterized by a novel technique which consists of bronchoalveolar lavage via the orotracheal route. Guinea pigs were sensitized twice at 2-week intervals with ovalbumin in silica and Bordetella pertussis. Two weeks after the booster sensitization all guinea pigs showed an acute decrease of tidal volume under CO2-forced respiration 5-15 min after antigen challenge. In contrast 42 out of 68 (= 62%) screened guinea pigs exhibited airway late phase response between 4-10 h after aerosol antigen challenge. During a subsequent cross-over study methylprednisolone (twice at 16 and 1 h before ovalbumin) did not significantly interfere with the acute response. In contrast the airway late phase response as well the associated eosinophil influx into the bronchoalveolar lavage were attenuated by the steroid. In conclusion, the sensitization procedure in combination with the novel method for monitoring airway function allowed measurement of a reproducible airway late phase response in about 60% of sensitized guinea pigs. The sensitivity of exclusively the late phase response and eosinophil influx to treatment with a glucocorticoid not only correlates this model with clinical pharmacotherapy but also strengthens the inflammatory nature of this model.
Heuer
H O
HO
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim/Rhein, Germany.
Wenz
B
B
Jennewein
H M
HM
Urich
K
K
D000276:Adjuvants, Immunologic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001886:Bordetella pertussis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018592:Cross-Over Studies; D006168:Guinea Pigs; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012822:Silicon Dioxide
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D012822:Silicon Dioxide; D010047:Ovalbumin; D008775:Methylprednisolone