A Th17- and Th2-skewed Cytokine Profile in Cystic Fibrosis Lungs Represents a Potential Risk Factor for Pseudomonas aeruginosa Infection

K Tiringer, A Treis, P Fucik, M Gona… - American journal of …, 2013 - atsjournals.org
K Tiringer, A Treis, P Fucik, M Gona, S Gruber, S Renner, E Dehlink, E Nachbaur, F Horak…
American journal of respiratory and critical care medicine, 2013atsjournals.org
Rationale: 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. Objectives: 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 …
Rationale: 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.
Objectives: 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.
Measurements and Main 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.
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