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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

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Abstract

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 theo-phylline 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.

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ACKNOWLEDGMENTS

The authors are grateful to the pulmonologists of the Minsk Clinical Consultative and Diagnostic Center E.I. Talabayeva and A.V. Plastinina for their assistance in this study.

Funding

The study was supported by the Belarusian State Scientific Program “Fundamental and Applied Sciences for Medicine” (task no. 2.56).

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Authors and Affiliations

  1. Belarusian State Medical University, pr. Dzerzhinskogo, 83, 220116, Minsk, Belarus

    A. G. Kadushkin, A. D. Tahanovich, T. S. Kolesnikova & E. V. Khadasouskaya

  2. Republican Scientific and Practical Center of Pediatric Oncology, Hematology and Immunology, ul. Frunzenskaya 43, 223053, Borovlyani, Minsk oblast, Belarus

    L. V. Movchan & T. V. Shman

Authors
  1. A. G. Kadushkin
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  5. E. V. Khadasouskaya
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Correspondence to A. G. Kadushkin.

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COMPLIANCE WITH ETHICAL STANDARDS

The study was approved by the Biomedical Ethics Committee of Belarusian State Medical University (Protocol no. 8, January 21, 2019). All patients were informed about the goals, objectives, research methodology and gave written voluntary consent to participate in it.

CONFLICT OF INTEREST

The authors declare that they have no conflict of inte-rest.

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Translated by A. Medvedev

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Kadushkin, A.G., Tahanovich, A.D., Movchan, L.V. et al. 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. Biochem. Moscow Suppl. Ser. B 15, 337–344 (2021). https://doi.org/10.1134/S1990750821040053

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