A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection.

Abstract

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.

• Authors: Kerstin Tiringer, Angela Treis, Petra Fucik, Mia Gona, Saskia Gruber, Sabine Renner, Eleonora Dehlink, Edith Nachbaur, Friedrich Horak, Peter Jaksch, Gerd Döring, Reto Crameri, Andreas Jung, Mascha K Rochat, Marcus Hörmann, Andreas Spittler, Walter Klepetko, Cezmi A Akdis, Zsolt Szépfalusi, Thomas Frischer, Thomas Eiwegger
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 187 Issue 6 Pg. 621-9 (Mar 15 2013) ISSN: 1535-4970 [Electronic] United States
• PMID: 23306544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interferon-gamma

Topics

• Adolescent
• Bronchoalveolar Lavage Fluid
• Child
• Child, Preschool
• Cystic Fibrosis (metabolism)
• Cytokines (metabolism)
• Female
• Humans
• Interferon-gamma (metabolism)
• Male
• Prognosis
• Prospective Studies
• Pseudomonas Infections (metabolism)
• Pseudomonas aeruginosa
• Th17 Cells (metabolism)
• Th2 Cells (metabolism)