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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.

biomedicinskaâ himiâ

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