Pulmonary T(H)2 response in Pseudomonas aeruginosa-infected patients with cystic fibrosis.
BACKGROUND
Pseudomonas aeruginosa infection determines the course of cystic fibrosis (CF) lung disease. Studies in human peripheral blood indicate that P aeruginosa infection is associated with a predominant T(H)2 immune response, whereas T(H)1 responses are accompanied by a better pulmonary outcome.


OBJECTIVE
Analyses of peripheral blood may not correspond directly with the local pulmonary immune response. Therefore, we asked whether the T(H)1/T(H)2 response is altered in bronchoalveolar lavage fluid from P aeruginosa-infected patients with CF.


METHODS
Bronchoalveolar lavage fluid was obtained from 12 patients with CF chronically infected with P aeruginosa, 11 noninfected patients with CF, and 8 healthy controls. Pulmonary CXCR3(+) (T(H)1) and CCR4(+) (T(H)2) expressing CD4(+) and CD8(+) lymphocytes were quantified by flow cytometry. Levels of T(H)1-associated (IL-2, IFN-gamma, IFN-gamma inducible T cell-alpha chemoattractant, Monokine induced by IFN-gamma, IFN-gamma inducible protein of 10 kd) and T(H)2-associated (IL-4, IL-5, IL-10, thymus and activation-regulated chemokine [TARC], macrophage-derived chemokine) cytokines and chemokines and a panel of proinflammatory molecules were quantified at the protein level. Chemokines mRNA levels were assessed by real time RT-PCR.


RESULTS
P aeruginosa-infected patients with CF had significantly higher levels of pulmonary CCR4(+)CD4(+) (T(H)2) cells, IL-4, IL-13, and TARC and lower levels of IFN-gamma compared with noninfected patients with CF and healthy controls. Bronchoalveolar lavage fluid levels of IL-4, IL-13, and TARC correlated inversely with FEV(1) in P aeruginosa-infected patients with CF.


CONCLUSIONS
These results reveal the prevalence of a pulmonary T(H)2 immune response in P aeruginosa-infected patients with CF. The modulation of the pulmonary T(H)2 response in P aeruginosa infection may be an option for the treatment of P aeruginosa lung disease in patients with CF.
Hartl
Dominik
D
Children's Hospital of the Ludwig-Maximilians-University of Munich, Munich, Germany.
Griese
Matthias
M
Kappler
Matthias
M
Zissel
Gernot
G
Reinhardt
Dietrich
D
Rebhan
Christian
C
Schendel
Dolores J
DJ
Krauss-Etschmann
Susanne
S
D000293:Adolescent; D000328:Adult; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000032:analysis; D002648:Child; D003550:Cystic Fibrosis / Q000276:immunology*; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008168:Lung / Q000276:immunology*; D008297:Male; D011552:Pseudomonas Infections / Q000276:immunology*; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
C106230:CCL17 protein, human; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D018793:Interleukin-13; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4