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

• Published in: Journal of allergy and clinical immunology Vol. 112; no. 1; pp. 37 - 44
• Main Authors: Mastruzzo, Claudio, Greco, Lucia Roberta, Nakano, Koichi, Nakano, Atsuko, Palermo, Filippo, Pistorio, Maria Provvidenza, Salinaro, Elisa Trovato, Jordana, Manel, Dolovich, Jerry, Crimi, †Nunzio, Vancheri, Carlo
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-07-2003; Elsevier; Elsevier Limited
• Subjects: Administration, Intranasal; Adult; Allergies; Asthma; Biological and medical sciences; budesonide; Budesonide - administration & dosage; CD4 T cells; CD8 T cells; Chronic Disease; Cytokines - analysis; Ent. Stomatology; Eosinophils - drug effects; Eosinophils - physiology; epithelial remodeling; Female; Humans; IL-4; IL-5; Immunohistochemistry; Lymphocytes; Male; Medical sciences; Middle Aged; Nasal Mucosa - drug effects; Nasal Mucosa - pathology; Nasal Mucosa - physiopathology; Nasal polyps; Nasal Polyps - drug therapy; Nasal Polyps - immunology; Nasal Polyps - pathology; Nose; Pharmacology. Drug treatments; Studies; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; TGF; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - physiology; budesonide; TGF; NP; epithelial remodeling; IL-4; IL-5; CD4 T cells; Nasal polyps; CD8 T cells; NM; Budesonide; Upper respiratory tract; Transforming growth factor β; Mucosa; Route of administration; Remodeling; Nose; T-Lymphocyte; TGF-β; Mechanism of action; Polyp; Human; Corticosteroid; Immune response; Antiinflammatory agent; Cytokine; Immune regulation; Inflammation; Intranasal administration; Epithelium; Chemotherapy; Treatment
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2003.1586

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 mm2 to 39.9 ± 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-γ, IL-12, and TGF-β 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-γ+ and IL-12+ cells remained unchanged. In addition, we found that the density of TGF-β+ 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-β. (J Allergy Clin Immunol 2003;112:37-44.)