Pulmonary T(H)2 response in Pseudomonas aeruginosa-infected patients with cystic fibrosis.

Authors: Hartl, D  Griese, M  Kappler, M  Zissel, G  Reinhardt, D  Rebhan, C  Schendel, DJ  Krauss-Etschmann, S 
Citation: Hartl D, etal., J Allergy Clin Immunol. 2006 Jan;117(1):204-11. Epub 2005 Nov 28.
Pubmed: (View Article at PubMed) PMID:16387607
DOI: Full-text: DOI:10.1016/j.jaci.2005.09.023

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. CONCLUSION: 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.


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RGD ID: 4145500
Created: 2010-11-05
Species: All species
Last Modified: 2010-11-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.