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A Th17-/Th2-skewed Cytokine profile in cystic fibrosis lungs represents a potential risk factor for pseudomonas aeruginosa infection


Tiringer, Kerstin; Treis, Angela; Fucik, Petra; Gona, Mia; Gruber, Saskia; Renner, Sabine; Dehlink, Eleonora; Nachbaur, Edith; Horak, Friedrich; Jaksch, Peter; Döring, Gerd; Crameri, Reto; Jung, Andreas; Rochat, Mascha K; Hörmann, Marcus; Spittler, Andreas; Klepetko, Walter; Akdis, Cezmi A; Szépfalusi, Zsolt; Frischer, Thomas; Eiwegger, Thomas (2013). A Th17-/Th2-skewed Cytokine profile in cystic fibrosis lungs represents a potential risk factor for pseudomonas aeruginosa infection. American Journal of Respiratory and Critical Care Medicine, 187(6):621-629.

Abstract

RATIONALE: Cystic Fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. P. 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±5.9y) and non-CF controls (n=9; 5.9±4.3y;). Memory responses to A. fumigatus and P. aeruginosa were monitored. HR-CT-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 (IL5, IL13), Th17 (IL17A) and Th17-related cytokines (IL1β, IL6) were significantly up-regulated in airways of CF patients. IL17A, IL13 and IL5 were significantly higher in BALF of symptomatic as compared to clinically asymptomatic CF patients. IL17A and IL5 correlated with the percentage of neutrophils in BALF (r=0.41, p<0.05 and r=0.46, p<0.05, respectively). Th17-associated (IL17A, IL6, IL1β, IL8) and Th2-associated cytokines/chemokines (IL5, IL13, TARC/CCL17), but not IFNγ levels, significantly correlated with HR-CT-changes (Helbich-score; p<0.05). P. aeruginosa- and A. fumigatus-specific T-cells from CF patients displayed significantly higher IL5 and IL17A mRNA expression. IL17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months. CONCLUSION: We propose a role for Th17 and Th2 T-cells in chronic inflammation in lungs of CF patients. A high concentration of these cytokines/chemokines in CF airways precedes infection with P. aeruginosa.

Abstract

RATIONALE: Cystic Fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. P. 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±5.9y) and non-CF controls (n=9; 5.9±4.3y;). Memory responses to A. fumigatus and P. aeruginosa were monitored. HR-CT-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 (IL5, IL13), Th17 (IL17A) and Th17-related cytokines (IL1β, IL6) were significantly up-regulated in airways of CF patients. IL17A, IL13 and IL5 were significantly higher in BALF of symptomatic as compared to clinically asymptomatic CF patients. IL17A and IL5 correlated with the percentage of neutrophils in BALF (r=0.41, p<0.05 and r=0.46, p<0.05, respectively). Th17-associated (IL17A, IL6, IL1β, IL8) and Th2-associated cytokines/chemokines (IL5, IL13, TARC/CCL17), but not IFNγ levels, significantly correlated with HR-CT-changes (Helbich-score; p<0.05). P. aeruginosa- and A. fumigatus-specific T-cells from CF patients displayed significantly higher IL5 and IL17A mRNA expression. IL17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months. CONCLUSION: We propose a role for Th17 and Th2 T-cells in chronic inflammation in lungs of CF patients. A high concentration of these cytokines/chemokines in CF airways precedes infection with P. aeruginosa.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:28 Mar 2013 10:10
Last Modified:05 Apr 2016 16:39
Publisher:American Thoracic Society
ISSN:1073-449X
Publisher DOI:https://doi.org/10.1164/rccm.201206-1150OC
PubMed ID:23306544

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