title: A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection.
abstract: BACKGROUND
  Cystic fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. Pseudomonas aeruginosa represents a risk factor for deterioration of lung function and reduced life expectancy.
  
  
  OBJECTIVE
  To assess T-cell cytokine/chemokine production in clinically stable children with CF and evaluate the association between T-cell subtypes and susceptibility for infection with P. aeruginosa.
  
  
  METHODS
  T-cell cytokine/chemokine profiles were measured in bronchoalveolar lavage fluid (BALF) from children with CF (n = 57; 6.1 ± 5.9 yr) and non-CF control subjects (n = 18; 5.9 ± 4.3 yr). Memory responses to Aspergillus fumigatus and P. aeruginosa were monitored. High-resolution computed tomography-based Helbich score was assessed. In a prospective observational trial the association between BALF cytokine/chemokine profiles and subsequent infection with P. aeruginosa was studied.
  
  
  RESULTS
  Th1- (INF-γ), Th2- (IL-5, IL-13), Th17- (IL-17A), and Th17-related cytokines (IL-1β, IL-6) were significantly up-regulated in airways of patients with CF. IL-17A, IL-13, and IL-5 were significantly higher in BALF of symptomatic as compared with clinically asymptomatic patients with CF. IL-17A and IL-5 correlated with the percentage of neutrophils in BALF (r = 0.41, P < 0.05 and r = 0.46, P < 0.05, respectively). Th17- (IL-17A, IL-6, IL-1β, IL-8) and Th2-associated cytokines and chemokines (IL-5, IL-13, TARC/CCL17), but not IFN-γ levels, significantly correlated with high-resolution computed tomography changes (Helbich score; P < 0.05). P. aeruginosa- and A. fumigatus-specific T cells from patients with CF displayed significantly higher IL-5 and IL-17A mRNA expression. IL-17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months.
  
  
  CONCLUSIONS
  We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Tiringer
authors.forename: Angela
authors.initials: A
authors.lastname: Treis
authors.forename: Petra
authors.initials: P
authors.lastname: Fucik
authors.forename: Mia
authors.initials: M
authors.lastname: Gona
authors.forename: Saskia
authors.initials: S
authors.lastname: Gruber
authors.forename: Sabine
authors.initials: S
authors.lastname: Renner
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dehlink
authors.forename: Edith
authors.initials: E
authors.lastname: Nachbaur
authors.forename: Friedrich
authors.initials: F
authors.lastname: Horak
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.forename: Gerd
authors.initials: G
authors.lastname: Döring
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Mascha K
authors.initials: MK
authors.lastname: Rochat
authors.forename: Marcus
authors.initials: M
authors.lastname: Hörmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szépfalusi
authors.forename: Thomas
authors.initials: T
authors.lastname: Frischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiwegger
mesh_terms: D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D058504:Th17 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007371:Interferon-gamma