Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs.
1. Guinea-pigs were sensitized with 3 injections of ovalbumin (OA) (1 or 10 micrograms per animal) using Al(OH)3 and pertussis vaccine as adjuvants at two week intervals. 2. Sensitized guinea-pigs were challenged with an aerosol of OA (0.1%) over a one hour period and both airway reactivity and cellular content of bronchoalveolar lavage (BAL) fluid were assessed at intervals for up to 7 days. 3. Guinea-pigs sensitized with 1 microgram of ovalbumin responded to an aerosol of OA with increased pulmonary airway eosinophilia, which was evident 1 day after challenge and was present for up to 7 days. Airway hyperreactivity was not detectable in these animals. 4. Guinea-pigs sensitized with 10 micrograms of ovalbumin responded to an aerosol of OA with increased pulmonary airway neutrophilia and eosinophilia and with increased airway reactivity which was maximal between 8 and 24 h after exposure to OA. 5. Depletion of circulating platelets or neutrophils, by use of selective antisera, did not alter either the magnitude of eosinophilia or the intensity of airway reactivity in sensitized guinea-pigs (10 micrograms) exposed to an aerosol of OA. 6. Pretreatment of sensitized guinea-pigs (10 micrograms) for 6 days with AH 21-132, aminophylline, dexamethasone or ketotifen inhibited pulmonary airway eosinophilia, but did not diminish airway hyperreactivity. Neither eosinophil accumulation nor development of airway hyperreactivity was influenced by treatment with mepyramine or salbutamol over a 6 day period before OA inhalation. 7. Although eosinophilia may occur in association with increased airway reactivity in this animal model, there is no evidence of a causal relationship.
Sanjar
S
S
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Aoki
S
S
Kristersson
A
A
Smith
D
D
Morley
J
J
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D015237:Dinoprost / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010567:Pertussis Vaccine / Q000276:immunology; D011817:Rabbits; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology
D010567:Pertussis Vaccine; D006632:Histamine; D010047:Ovalbumin; D015237:Dinoprost