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
| العنوان: | 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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| المؤلفون: | Tatiana Shman, A V Khadasouskaya, Aliaksei Kadushkin, Anatoliy Tahanovich, T S Kolesnikova, Liudmila Movchan |
| المصدر: | Biomeditsinskaya Khimiya. 67:352-359 |
| بيانات النشر: | Institute of Biochemistry, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Budesonide, business.industry, medicine.medical_treatment, General Medicine, Azithromycin, Pharmacology, General Biochemistry, Genetics and Molecular Biology, Proinflammatory cytokine, Killer Cells, Natural, Pulmonary Disease, Chronic Obstructive, Cytokine, Theophylline, medicine, Cytokines, Humans, Tumor necrosis factor alpha, Interleukin 8, business, Glucocorticoids, Interleukin 4, Whole blood, medicine.drug |
| الوصف: | 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.Khronicheskaia obstruktivnaia bolezn' legkikh (KhOBL) kharakterizuetsia snizhennoĭ chuvstvitel'nost'iu kletok k protivovospalitel'nym éffektam gliukokortikosteroidov (GKS). Izvestno, chto teofillin v nizkoĭ kontsentratsii i azitromitsin mogut vliiat' na molekuliarnye mekhanizmy razvitiia steroidorezistentnosti. Tsel'iu nastoiashchego issledovaniia byla otsenka sposobnosti azitromitsina i teofillina usilivat' protivovospalitel'noe deĭstvie GKS na produktsiiu tsitokinov NK i NKT-podobnymi kletkami krovi patsientov s KhOBL. Kletki tsel'noĭ krovi patsientov c KhOBL (n=21) inkubirovali v prisutstvii budesonida (10 nM), azitromitsina (10 mkg/ml), teofillina (1 mkM) ili ikh kombinatsiĭ i stimulirovali forbol-miristat-atsetatom (50 ng/ml). Vnutrikletochnuiu produktsiiu provospalitel'nykh tsitokinov v NK (CD3-CD56+) i NKT-podobnykh (CD3+CD56+) kletkakh krovi analizirovali metodom protochnoĭ tsitometrii. Budesonid snizhal sintez interleĭkina 4 (IL-4), CXCL8, faktora nekroza opukholi α (FNOα) NK i NKT-podobnymi kletkami, a takzhe produktsiiu interferona γ (IFNγ) NK kletkami. Azitromitsin podavlial sintez IL-4 i CXCL8 NK i NKT-podobnymi kletkami, a teofillin ingibiroval produktsiiu IL-4 étimi limfotsitami. Sochetanie azitromitsina i budesonida okazyvalo bolee vyrazhennoe ingibiruiushchee vozdeĭstvie na produktsiiu IL-4 i CXCL8 NK i NKT-podobnymi kletkami, chem deĭstvie liubogo iz étikh preparatov. Kombinatsiia teofillina i budesonida supressirovala sintez IL-4 i CXCL8 NK i NKT-podobnymi kletkami, a takzhe produktsiiu FNOα i IFNγ NK kletkami bolee znachitel'no, chem odin budesonid. Poluchennye dannye demonstriruiut preimushchestva kombinirovannogo ispol'zovaniia GKS sovmestno s teofillinom v nizkoĭ kontsentratsii libo azitromitsinom dlia podavleniia vospalitel'nogo protsessa u patsientov s KhOBL. |
| تدمد: | 2310-6905 2310-6972 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d36079c8c24e426e1be1cf3658992ce3Test https://doi.org/10.18097/pbmc20216704352Test |
| رقم الانضمام: | edsair.doi.dedup.....d36079c8c24e426e1be1cf3658992ce3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23106905 23106972 |
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