EXPRESSION OF IL-4, C-EPSILON RNA, AND I-EPSILON RNA IN THE NASAL-MUCOSA OF PATIENTS WITH SEASONAL RHINITIS - EFFECT OF TOPICAL CORTICOSTEROIDS

Background: Nasal allergen provocation has demonstrated that allergen- induced rhinitis is associated with an increase in local IL-4 mRNA and IgE heavy chain (C epsilon) and IgE heavy chain promoter (I epsilon) RNA and that pretreatment with topical glucocorticosteroids inhibits t he increase in these transcripts. Objective; This study was undertaken ta determine whether observations made after acute allergen provocati on can be extended to the case of chronic exposure experienced during the pollen season. Methods: Biopsy specimens were obtained from the in ferior turbinate of 33 pollen-sensitive subjects with allergic rhiniti s before and during pollen season. Patients were randomized in a doubl e-blind fashion and treated with either topical steroids (200 mu g flu ticasone propionate twice daily; n = 16) or matched placebo nasal spra g (n = 17) before the pollen season. Alkaline phospatase anti-alkaline phosphatase immunocytochemistry was used to identify B cells (CD20(+) ), and in situ hybridization was used to detect IL-4, C epsilon and I epsilon RNA(+) cells. Results: Baseline examination revealed IL-4 and C epsilon RNA but virtually no I epsilon RNA(+) cells in the nasal muc osa. Analysis revealed a significant difference in the expression of C epsilon and I epsilon RNA(+) cells (p < 0.001). Biopsy specimens take n after antigen exposure exhibited highly significant increases in pla cebo-treated (p < 0.001) but not steroid-treated patients. In both gro ups, the number of CD20(+) cells was unchanged when preexposure and po stexposure biopsy specimens were compared. Conclusions: These results show strong support for the hypothesis that IgE class switching occurs locally within the nasal mucosa of subjects with seasonal allergic rh initis and that this response can be inhibited through strategies dire cted against local IgE production.