title: Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation.
abstract: 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.
authors.affiliation: Department of Internal and Specialistic Medicine, Section of Respiratory Diseases and Section of Infectious Diseases, University of Catania, Catania, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mastruzzo
authors.forename: Lucia Roberta
authors.initials: LR
authors.lastname: Greco
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakano
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakano
authors.forename: Filippo
authors.initials: F
authors.lastname: Palermo
authors.forename: Maria Provvidenza
authors.initials: MP
authors.lastname: Pistorio
authors.forename: Elisa Trovato
authors.initials: ET
authors.lastname: Salinaro
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Jerry
authors.initials: J
authors.lastname: Dolovich
authors.forename: Dagger Nunzio
authors.initials: DN
authors.lastname: Crimi
authors.forename: Carlo
authors.initials: C
authors.lastname: Vancheri
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D019819:Budesonide / Q000008:administration & dosage*; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009298:Nasal Polyps / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000502:physiology
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta; D019819:Budesonide