Experimentally induced nasal allergic responses.
To investigate the pathogenesis of allergic rhinitis, we developed a nasal challenge model in which we examined the early, late, and rechallenge responses to antigen provocation. In these three aspects of the allergic reaction the physiologic responses are associated with inflammatory mediator release. Whereas the early response appears to be related mainly to mast cell activation and mediator release, the late reaction involves a different pattern of mediator release and an inflammatory cell influx, consisting of basophils, neutrophils, and eosinophils. Rechallenge with antigen 11 hours later results in an augmented immediate response. Pretreatment with aspirin reduces the levels of cyclooxygenase metabolites in nasal secretions without affecting the immediate physiologic response to antigen or the expected increase in the levels of histamine, N-alpha-tosyl-L-arginine methyl ester-esterase activity, and leukotriene C4. Pretreatment with systemic steroids does not affect the early allergic response, but significantly reduces mediator release during the late and rechallenge responses. The influx of eosinophils is inhibited by pretreatment with systemic steroids, but neutrophil influx is not. In contrast, pretreatment with topical steroids blocks the early response and the late and rechallenge responses. Influx of all cell types, including the neutrophil, was prevented. These studies show unequivocally that an inflammatory process follows the initial response to antigen and that this inflammation is affected by drugs important in the treatment of chronic allergic disease. We speculate that understanding allergic inflammation will lead to new therapeutic development.
Walden
S M
SM
Department of Medicine, Johns Hopkins University, Baltimore, MD.
Proud
D
D
Bascom
R
R
Lichtenstein
L M
LM
Kagey-Sobotka
A
A
Adkinson
N F
NF
Naclerio
R M
RM
D000941:Antigens / Q000276:immunology*; D001241:Aspirin / Q000494:pharmacology; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed; D008407:Mast Cells / Q000378:metabolism; D009299:Nasal Provocation Tests / Q000379:methods*; D011241:Prednisone / Q000494:pharmacology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*
D000941:Antigens; D005446:Fluocinolone Acetonide; C007734:flunisolide; D001241:Aspirin; D011241:Prednisone