Journal Article

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

Gruber, Saskia, Klepetko, Walter, Horak, Friedrich, Crameri, Reto, Nachbaur, Edith, Dehlink, Eleonora, Renner, Sabine, Jaksch, Peter, Jung, Andreas, Döring, Gerd, Akdis, Cezmi A., Spittler, Andreas, Szépfalusi, Zsolt, Treis, Angela, Hörmann, Marcus, Fucik, Petra, Gona, Mia, Rochat, Mascha K., Frischer, Thomas, Tiringer, Kerstin, Eiwegger, Thomas

2013

Overview

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. 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. 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. 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. 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.

• Publisher: American Thoracic Society,Oxford University Press
• Subject: Adolescent / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Antigens / Biological and medical sciences / Bronchoalveolar Lavage Fluid / Bronchoscopy / Chemokines / Child / Child, Preschool / Cystic fibrosis / Cystic Fibrosis - metabolism / Cytokines / Cytokines - metabolism / Errors of metabolism / Female / General aspects / Human infectious diseases. Experimental studies and models / Humans / Infections / Infectious diseases / Inflammation / Intensive care medicine / Interferon-gamma - metabolism / Lavage / Lungs / Lymphocytes / Male / Medical sciences / Metabolic diseases / Miscellaneous hereditary metabolic disorders / Neutrophils / Polymerase chain reaction / Prognosis / Prospective Studies / Pseudomonas aeruginosa / Pseudomonas Infections - metabolism / Th17 Cells - metabolism / Th2 Cells - metabolism / Tomography