Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in COPD.
BACKGROUND
Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the anti-inflammatory mechanism of SFC remains unclear. In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4+CD25+Foxp3+ regulatory T cells (Foxp3+Tregs) after SFC therapy.


METHODS
Twenty-one patients with moderate or severe COPD received treatment with 50/500 μg of SFC twice a day for 12 weeks. Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test. The number of neutrophils, monocytes and lymphocytes in induced sputum were counted. Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA. The proportion of Foxp3+Tregs in the total CD4+ T cell of the peripheral blood was determined by flow cytometry. The relationship between IL-17A levels and the percentage of Foxp3+Tregs was analyzed by statistical analysis.


RESULTS
After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased. The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased. Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged. The proportion of Foxp3+Tregs in the total CD4+T cell population in the peripheral blood was drastically higher than that before treatment. The level of IL-17A was negatively correlated with the proportion of Foxp3+Tregs in CD4+T cells.


CONCLUSIONS
SFC can reduce the levels of inflammatory factors and improve symptoms of COPD. The levels of inflammatory factors are associated with the variation of Foxp3+Tregs in COPD.


BACKGROUND
This study was registered with http://www.chictr.org (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270.
Institute of Respiratory Diseases, the Second Hospital of the Third Military Medical University of China, 183 Xinqiao Street, Chongqing 400037, P. R. China.
Li
L
Yang
Qian-li
QL
Ma
Wei
W
Yao
Qiao
Q
Zhang
Hua-ping
HP
Chen
Guan-song
GS
Wang
Chang-zheng
CZ
Wang
D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage; D015704:CD4 Antigens / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D000068298:Fluticasone; D051858:Forkhead Transcription Factors / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D000068299:Salmeterol Xinafoate; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol