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

作者：Tiringer Kerstin; Treis Angela; Fucik Petra; Gona Mia; Gruber Saskia; Renner Sabine; Dehlink Eleonora; Nachbaur Edith; Horak Friedrich; Jaksch Peter; Doering Gerd; Crameri Reto; Jung Andreas; Rochat Mascha K; Hoermann Marcus; Spittler Andreas; Klepetko Walter; Akdis Cezmi A; Szep****si Zsolt; Frischer Thomas; Eiwegger Thomas^*

来源：American Journal of Respiratory and Critical Care Medicine, 2013, 187(6): 621-629.

DOI：10.1164/rccm.201206-1150OC

• T cell
• cystic fibrosis
• Pseudomonas aeruginosa
• IL-17
• bronchoalveolar lavage fluid

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Measurements and Main Results: Th1- (INF-gamma), Th2- (IL-5, IL-13), Th17- (IL-17A), and Th17-related cytokines (IL-1 beta, 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 %26lt; 0.05 and r = 0.46, P %26lt; 0.05, respectively). Th17- (IL-17A, IL-6, IL-1 beta, IL-8) and Th2-associated cytokines and chemokines (IL-5, IL-13, TARC/CCL17), but not IFN-gamma levels, significantly correlated with high-resolution computed tomography changes (Helbich score; P %26lt; 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. %26lt;br%26gt;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.

• 出版日期2013-3-15
• 单位河北医科大学