Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:112

Article

Mastruzzo, C ; Greco, LR ; Nakano, K ; Nakano, A ; Palermo, F ; Pistorio, MP ; Salinaro, ET ; Jordana, M ; Dolovich, J ; Crimi, N ; Vancheri, C

关键词: nasal polyps;    budesonide;    TGF-beta;    CD4 T cells;    CD8 T cells;    IL-4;    IL-5;    epithelial remodeling;   

DOI  :  10.1067/mai.2003.1586

来源: Elsevier

【 摘 要 】

Background: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. Objective: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. Methods: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. Results: First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. Conclusions: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta.

【 授权许可】

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