Pulmonary TH2 response in Pseudomonas aeruginosa–infected patients with cystic fibrosis

BackgroundPseudomonas 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 TH2 immune response, whereas TH1 responses are accompanied by a better pulmonary outcome.ObjectiveAnalyses of peripheral blood may not correspond directly with the local pulmonary immune response. Therefore, we asked whether the TH1/TH2 response is altered in bronchoalveolar lavage fluid from P aeruginosa–infected patients with CF.MethodsBronchoalveolar 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+ (TH1) and CCR4+ (TH2) expressing CD4+ and CD8+ lymphocytes were quantified by flow cytometry. Levels of TH1-associated (IL-2, IFN-γ, IFN-γ inducible T cell-α chemoattractant, Monokine induced by IFN-γ, IFN-γ inducible protein of 10 kd) and TH2-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.ResultsP aeruginosa–infected patients with CF had significantly higher levels of pulmonary CCR4+CD4+ (TH2) cells, IL-4, IL-13, and TARC and lower levels of IFN-γ compared with noninfected patients with CF and healthy controls. Bronchoalveolar lavage fluid levels of IL-4, IL-13, and TARC correlated inversely with FEV1 in P aeruginosa–infected patients with CF.ConclusionThese results reveal the prevalence of a pulmonary TH2 immune response in P aeruginosa–infected patients with CF. The modulation of the pulmonary TH2 response in P aeruginosa infection may be an option for the treatment of P aeruginosa lung disease in patients with CF.