[Population rearrangement of B-lymphocytes expressing chemokine receptors in patients with chronic obstructive pulmonary disease]. / Populiatsionnaia perestroika B-limfotsitov, ékspressiruiushchikh khemokinovye retseptory, u patsientov s khronicheskoi obstruktivnoi bolezn'iu legkikh.

To date, there are no drugs that can prevent progressive destruction of lung tissue and small airway fibrosis in patients with chronic obstructive pulmonary disease (COPD). Therefore, molecular mechanisms of this disease are being studied. The aim of this study was to determine the chemokine receptor expression pattern of B-lymphocytes from peripheral blood and airways of patients with COPD. Peripheral blood was collected from 51 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers. Seven smokers with COPD and 7 healthy smokers were recruited to undergo bronchoscopy with bronchoalveolar lavage (BAL). The expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 on the surface of blood and BAL B-lymphocytes was determined by flow cytometry. It was found that the percentage of blood B-lymphocytes expressing chemokine receptors CCR5 and CXCR3 was higher in smokers with COPD compared with healthy smokers and healthy non-smokers. The percentage of CD27⁺ B-cells expressing CCR5 and CXCR3 receptors exceeded the proportion of CD27⁻ B-lymphocytes expressing these receptors in peripheral blood of patients with COPD and healthy controls. In smoking patients with COPD, the percentage of BAL B-cells expressing receptors CCR5 and CXCR3 was also increased compared with healthy smokers. There were no differences in the percentage of B-lymphocytes expressing receptors CXCR4, CXCR5, CCR6, and CCR7 in both peripheral blood and BAL between smokers with COPD and healthy smokers. A greater percentage of CD27⁻ B-lymphocytes than CD27⁺ B-cells expressed receptors CXCR4, CXCR5, CCR6, and CCR7 in the peripheral blood of smokers with COPD and healthy controls. The results of this study indicate a modification in the chemokine receptor profile of B-lymphocytes in COPD.

Nortriptyline Modulates the Migration of Peripheral Blood Lymphocytes and Monocytes in Patients with Chronic Obstructive Pulmonary Disease.

In the present study, the effect of nortriptyline (1 and 10 µM), budesonide (10 nM) and their combination on the migration of peripheral blood lymphocytes and monocytes from patients with chronic obstructive pulmonary disease (COPD) towards chemokines CCL5 and CXCL10 was evaluated by flow cytometry. Nortriptyline (10 µM), both alone and in combination with budesonide, inhibited the migration of T helper cells, cytotoxic T lymphocytes, NK cells and B lymphocytes towards CCL5 and CXCL10, as well as enhanced monocyte migration towards these chemokines. The combination of nortriptyline (1 µM) and budesonide suppressed the chemotaxis of lymphocyte subpopulations towards CXCL10, but not towards CCL5, more effectively than budesonide alone. The combination of nortriptyline (10 µM) and budesonide inhibited the migration of lymphocyte subpopulations towards CCL5 and CXCL10 and activated monocyte chemotaxis towards both chemokines more effectively than budesonide alone. The results of this study demonstrate the ability of nortriptyline alone to modulate the migration of peripheral blood lymphocytes and monocytes from patients with COPD and to potentiate the effects of budesonide.

[The effect of glucocorticoids in combination with azithromycin or theophylline on cytokine production by NK and NKT-like blood cells of patients with chronic obstructive pulmonary disease]. / Vliianie gliukokortikosteroidov pri ikh sovmestnom primenenii s azitromitsinom ili teofillinom na produktsiiu tsitokinov NK i NKT-podobnymi kletkami krovi patsientov s khronicheskoi obstruktivnoi bolezn'iu legkikh.

Chronic obstructive pulmonary disease (COPD) is characterized by reduced sensitivity of cells to the anti-inflammatory effects of glucocorticoids (GCs). Azithromycin and a low dose theophylline have a significant impact on molecular mechanisms leading to corticosteroid resistance. The aim of this study was to evaluate the ability of azithromycin and theophylline to enhance the anti-inflammatory effects of GCs on the production of cytokines by NK and NKT-like blood cells of COPD patients. Whole blood cells from COPD patients (n=21) were incubated in the presence of budesonide (10 nM), azithromycin (10 µg/mL), theophylline (1 µM), or their combinations and stimulated with phorbol myristate acetate (50 ng/mL). Intracellular production of proinflammatory cytokines in NK (CD3-CD56+) and NKT-like (CD3+CD56+) blood cells was analyzed by flow cytometry. Budesonide reduced synthesis of interleukin 4 (IL-4), CXCL8, tumor necrosis factor α (TNFα) by NK and NKT-like cells, as well as production of interferon γ (IFNγ) by NK cells. Azithromycin suppressed production of IL-4 and CXCL8 by NK and NKT-like cells, and theophylline inhibited IL-4 synthesis by these lymphocytes. The combination of azithromycin and budesonide had a more pronounced inhibitory effect on the production of IL-4 and CXCL8 by NK and NKT-like cells than the effect of these drugs alone. The combination of theophylline and budesonide suppressed synthesis of IL-4 and CXCL8 by NK and NKT-like cells, as well as the production of TNFα and IFNγ by NK cells stronger than budesonide alone. The obtained results demonstrate the benefits for the combined use of GCs with theophylline at a low dose or azithromycin to suppress the inflammatory process in patients with COPD.

[Clinical and laboratory parameters in assessing the risk of exacerbations in chronic obstructive pulmonary disease].

AIM: To estimate the significance of measuring the concentrations of cytokines and immunoglobulins and the relative counts of lymphocyte subpopulations in peripheral blood, as well as clinical parameters in patients with chronic obstructive pulmonary disease (COPD) in order to assess the risk of exacerbations. SUBJECTS AND METHODS: Thirty-seven patients with COPD were examined. A study group consisted of 31 patients. Patients with rare exacerbations were assigned to those who had no or one case; patients with frequent exacerbations were those who had two or more cases a year after examination. A prognostic model was created using the binary logistic regression analysis. RESULTS: A significant statistical model was developed as a regression equation involving 4 indicators (vascular endothelial growth factor, C-reactive protein, CAT scores, and number of exacerbations in the previous year). This mathematical model can predict frequent exacerbations in next year with a sensitivity of 94.1% and a specificity of 80%. CONCLUSION: The mathematical model created to estimate the risk of frequent exacerbations may be used to elaborate adequate individual treatment regimens for both smoking and non-smoking patients with COPD.