Fluticasone impact on airway dendritic cells in smokers: a randomized controlled trial

被引:7
作者
Lommatzsch, Marek [1 ,3 ]
Kraeft, Ulrike [1 ]
Troebs, Laura [1 ]
Garbe, Katharina [1 ]
Bier, Andrea [1 ]
Stoll, Paul [1 ]
Klammt, Sebastian [2 ]
Kuepper, Michael [1 ]
Bratke, Kai [1 ]
Virchow, Johann Christian [1 ]
机构
[1] Univ Rostock, Dept Pneumol, D-18057 Rostock, Germany
[2] Univ Rostock, Dept Trop Med & Infect Dis, D-18057 Rostock, Germany
[3] Univ Rostock, Abt Pneumol & Internist Intens Med, Zentrum Innere Med, D-18057 Rostock, Germany
来源
RESPIRATORY RESEARCH | 2013年 / 14卷
关键词
Smoking; Dendritic cells; Inhaled corticosteroids; OBSTRUCTIVE PULMONARY-DISEASE; SALMETEROL/FLUTICASONE PROPIONATE; ASTHMA; COPD; DIFFERENTIATION; ACCUMULATION; SUPPRESSES; SUBSETS; MUCOSA; BETA;
D O I
10.1186/1465-9921-14-114
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: Myeloid Dendritic cells are key drivers of inflammation in smoke-related lung diseases, whereas plasmacytoid DCs play a crucial role in the defense against infections. Effects of inhaled corticosteroids (ICS) on airway DCs in smokers are unknown. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 45 active cigarette smokers inhaled placebo, fluticasone or fluticasone plus salmeterol twice daily for 4 weeks. Bronchoalveolar lavage fluid DCs were analyzed using four-color flow cytometry before and after the inhalation period. In addition, fluticasone effects were tested on T-cell proliferation in co-cultures with blood myeloid DCs from smokers. Results: Inhalation of fluticasone plus salmeterol, but not fluticasone alone or placebo, reduced endobronchial concentrations of myeloid DCs (median decrease: 24%), macrophages (median decrease: 26%) and neutrophils (median decrease: 76%). In contrast, fluticasone reduced plasmacytoid DC concentrations independently of salmeterol. There were no changes in the expression of function-associated surface molecules on myeloid DC (such as CD1a, Langerin, BDCA-1, CD83 or CCR5) in all groups after treatment. Fluticasone (either alone or in combination with salmeterol) suppressed T-cell proliferation in co-cultures with blood myeloid DCs from smokers. Conclusions: Resistance to ICS monotherapy in smokers might in part be due to lacking effects on airway myeloid DCs, whereas the increased risk for infections during ICS therapy could be attributable to a reduction in plasmacytoid DCs. Combination therapy of fluticasone with salmeterol is associated with a reduction in airway myeloid DCs, but also airway macrophages and neutrophils.
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页数:10
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