title: Tregs and HLA-DR expression in sputum cells of COPD patients treated with tiotropium and formoterol.
abstract: Immune cells expressing the activation markers HLA-DR and regulatory T cells (Tregs) may be involved in the regulation of chronic inflammation in chronic obstructive pulmonary disease (COPD). In this study we analyzed native and activated cell profiles in sputum of 22 stable COPD patients receiving formoterol (F) or formoterol + tiotropium (F + T) for 3 months. Cells were isolated from induced sputum and were examined on Coulter flow cytometer using fluorescent antibodies specific for CD3, CD4, CD8, CD14, CD19, CD25, CD127, and HLA-DR antigens. Cell profiles and cell activation were assessed by analysis of HLA-DR, CD25, and CD127 co-expression in double-stained samples. Tregs were defined as CD4⁺CD25(high) CD127(low) cells. We found that the combined therapy significantly decreased the CD8⁺ cell number (p < 0.01). At baseline, HLA-DR was expressed in about 10 % of sputum T or B cells and a higher expression was found on monocytes. The HLA-DR expression on lymphocytes, but not monocytes, was significantly lower (p < 0.01) in patients treated with F + T. Fractions of activated [CD4⁺ CD25⁺] cells were also significantly lower in the combined therapy group, except for the subpopulation of CD4⁺CD25(high) CD127(low) cells which was not altered. We conclude that tiotropium in add-on therapy to formoterol affects Treg cell profiles and decreases HLA-DR expression in airway lymphocytes.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Bialystok, 15a Waszyngtona St., Bialystok, Poland, holow_sinai@hotmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Holownia
authors.forename: P
authors.initials: P
authors.lastname: Wielgat
authors.forename: A
authors.initials: A
authors.lastname: Stasiak-Barmuta
authors.forename: A
authors.initials: A
authors.lastname: Kwolek
authors.forename: P
authors.initials: P
authors.lastname: Jakubow
authors.forename: P
authors.initials: P
authors.lastname: Szepiel
authors.forename: E
authors.initials: E
authors.lastname: Chyczewska
authors.forename: J J
authors.initials: JJ
authors.lastname: Braszko
authors.forename: R M
authors.initials: RM
authors.lastname: Mroz
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002469:Cell Separation; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000627:therapeutic use*; D000068759:Formoterol Fumarate; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D013183:Sputum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000069447:Tiotropium Bromide
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D015703:Antigens, CD; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004983:Ethanolamines; D006684:HLA-DR Antigens; D012602:Scopolamine Derivatives; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide