Lack of late-phase airway responses in conscious guinea pigs after a variety of antigen challenges.
Guinea pigs were actively sensitized by parenteral injections of ovalbumin (OA), house dust extract (HD) or Ascaris suum extract (As) in a variety of multidose regimens. At least 3 weeks after the initial sensitization injection, aerosols of the appropriate antigen were administered to conscious guinea pigs in a double-chamber body plethysmograph. OA elicited the most consistent and intense bronchoconstriction (BC) as measured by decreases in specific airway conductance (sGAW). The airway responses to As were clearly separable into responders and nonresponders. HD produced essentially no BC. However, intense lacrimation and rhinorrhea occurred in all HD-sensitized, but not unsensitized, animals. No late-phase changes in sGAW or increased reactivity to other spasmogens were seen up to 8 h after any antigen challenge. Eosinophil influx of magnitude similar to that measured by 24 h post-antigen bronchoalveolar lavage (BAL) occurred with all the three antigens. Animals which did not bronchoconstrict to As experienced an equal or greater pulmonary eosinophilia as airway responders. The present data with HD and As suggest that acute BC in response to antigen provocation is not a prerequisite for the eventual pulmonary eosinophilia. The lack of late-phase airway reactions in these models raises a doubt in the direct extrapolation to airway responses in allergic human asthma. The acute lacrimation and rhinorrhea to HD may suggest utility as a model of allergic rhinitis.
Underwood
D C
DC
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Osborn
R R
RR
Hand
J M
JM
D000336:Aerosols; D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001200:Ascaris / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004391:Dust / Q000009:adverse effects; D004804:Eosinophils / Q000502:physiology; D006168:Guinea Pigs; D007958:Leukocyte Count; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015656:Respiratory Mechanics / Q000502:physiology
D000336:Aerosols; D000485:Allergens; D000941:Antigens; D004391:Dust; D010047:Ovalbumin