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Mechanism of topical glucocorticoid treatment of hay fever: IL-5 and eosinophil activation during natural allergen exposure are suppressed, but IL-4, IL-6, and IgE antibody production are unaffected

Doi : 10.1067/mai.2000.108430 

Hirohito Kita, Ronald K. Jorgensen, Charles E. Reed, Sandra L. Dunnette, Mark C. Swanson, Kathleen R. Bartemes, Diane Squillace, Judy Blomgren, Kay Bachman, Gerald J. Gleich

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Abstract

Background: Allergic rhinitis is traditionally defined as an IgE- and mast cell–mediated hypersensitivity reaction. Allergen challenge models suggest that cytokines and eosinophil mediators may also play roles. However, the causal relationship among inflammatory cells, their products, and patients’ symptoms during natural allergen exposure has not been established. Objective: We sought to elucidate the mechanisms of seasonal allergic rhinitis and the beneficial effects of topical glucocorticoids. Methods: Thirty patients with ragweed-induced hay fever and a strongly positive serologic test response for ragweed IgE antibody received budesonide nasal spray or placebo in a randomized, parallel, double-blind study. Nasal wash fluids and sera were collected before and during the hay fever season. The levels of inflammatory mediators and allergen-specific immunoglobulins were measured by immunoassay. The activation markers on blood eosinophils were quantitated by flow cytometry. Results: Compared with placebo-treated patients, budesonide-treated patients had strikingly reduced symptoms. In the placebo group, nasal symptoms correlated with nasal lavage fluid eosinophil-derived neurotoxin and IL-5 levels. At the season peak, the budesonide-treated group had significantly lower nasal fluid eosinophil-derived neurotoxin, IL-5, and soluble intracellular adhesion molecule-1 levels. In the treated group eosinophil expression of CD11b was suppressed at the season peak. In contrast, levels of IL-4 and IL-6 in nasal fluid and the seasonal increases in serum ragweed-specific IgE and nasal fluid IgA antibodies did not differ between groups. Conclusion: Eosinophilic inflammation plays a critical role in seasonal allergic rhinitis symptoms. One of the therapeutic effects of glucocorticoids is to suppress this inflammation. (J Allergy Clin Immunol 2000;106:521-9.)

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Keywords : Allergic rhinitis, topical budesonide, cytokines, eosinophils, adhesion molecules, IgE, secretory IgA

Abbreviations : EDN:, ICAM-1:, MBP:


Plan


 Supported in part by grants from Astra Pharmaceuticals (Westborough, Mass), grants from the National Institutes of Health (AI 34577 and AI 34486), and the Mayo Foundation.
 Reprint requests: Hirohita Kita, MD, Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905.


© 2000  Mosby, Inc. Tous droits réservés.
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Vol 106 - N° 3

P. 521-529 - septembre 2000 Retour au numéro
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