Effects of recombinant IFN-α2b on the phenotype of neutrophil granulocyte subpopulations in patients with COVID-19

Q4 Medicine Infektsionnye Bolezni Pub Date : 2022-01-01 DOI:10.20953/1729-9225-2022-1-43-51

I. Nesterova, V. Gorodin, G. Chudilova, V. N. Chapurina, V. A. Matushkina, R.Yu. Gabdrakhmanova, L. Lomtatidze, S. Kovaleva, V. V.V.Malinovskaya, Т. Semenenko

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引用次数: 3

Abstract

Investigation of molecular mechanisms associated with interferon (IFN) production and receptor function of neutrophil granulocytes (NGs) in COVID-19 is highly relevant because it can be promising in the search for new therapeutic strategies targeting NGs and their reactivity to restore and strengthen the innate immune response against SARS-CoV-2. Objective. To assess the effects of recombinant IFN-α2b on the phenotype of CD16+IFNα/βR1–CD119+, CD16+IFNα/βR1+CD119–, and CD16+IFNα/βR1+CD119+ NGs from peripheral blood of patients with COVID-19 in an in vitro experiment. Patients and methods. We analyzed blood samples from 31 patients with a mean age of 61 years (range: 57;71 years) with moderate COVID-19. We assessed the number of CD16+IFNα/βR1–CD119+, CD16+IFNα/βR1+CD119–, and CD16+IFNα/βR1+CD119+ NGs, receptor density (FC 500, ‘Beckman Coulter,’ USA), phagocytic activity of NGs before and after incubation with recombinant IFN-α2b. We also measured serum levels of several cytokines, including IFNα, IFNγ, IL-6, IL-8 (ELISA, ‘Vektor-Best’ LLC). The control group comprised 22 adult healthy individuals with a mean age of 58 years (range: 57; 70 years). Results. Patients with moderate COVID-19 demonstrated low serum levels of IFNα and IFNγ along with elevated levels of IL-6 and IL-8. We observed transformation of 3 phenotypes among NG subpopulations: CD16+IFNα/βR1–CD119+, CD16+IFNα/βR1+CD119-, and CD16+IFNα/βR1+CD119+. We observed positive remodulating effects of recombinant IFN-α2b on the number and phenotype of NG subpopulations and their phagocytic activity in our in vitro experiment. Conclusion. Recombinant IFN-α2b demonstrated positive effects in in vitro experiments; therefore, it can be considered in the future as a potential therapeutic tool for moderate COVID-19. Restoration of type I IFN might be an effective treatment option for COVID-19, because it can promote faster virus elimination, restore normal functioning of the IFN system, and have positive regulatory effects on the phenotype of NG subpopulations. Key words: neutrophil granulocytes, subpopulations, COVID-19, phenotype, recombinant interferon α2b

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重组IFN-α2b对COVID-19患者中性粒细胞亚群表型的影响

研究与COVID-19中中性粒细胞(NGs)干扰素(IFN)产生和受体功能相关的分子机制具有重要意义，因为它可能有助于寻找针对NGs及其反应性的新治疗策略，以恢复和加强针对SARS-CoV-2的先天免疫应答。目标。目的:探讨重组IFN-α2b对新冠肺炎患者外周血CD16+IFNα/βR1 - CD119+、CD16+IFNα/βR1+CD119 -、CD16+IFNα/βR1+CD119+ NGs表型的影响。患者和方法。我们分析了31例平均年龄61岁(范围:57岁;71岁)的中度COVID-19患者的血液样本。我们评估了重组IFN-α2b孵育前后CD16+IFNα/βR1 - CD119+、CD16+IFNα/βR1+CD119 -和CD16+IFNα/βR1+CD119+ NGs的数量、受体密度(FC 500， ' Beckman Coulter '， '美国)、NGs的吞噬活性。我们还测量了几种细胞因子的血清水平，包括IFNα， IFNγ， IL-6, IL-8 (ELISA， ' vector - best ' LLC)。对照组包括22名健康成人，平均年龄58岁(范围:57岁;70年)。结果。中度COVID-19患者血清IFNα和IFNγ水平低，IL-6和IL-8水平升高。我们在NG亚群中观察到3种表型的转化:CD16+IFNα/βR1 - CD119+， CD16+IFNα/βR1+CD119-和CD16+IFNα/βR1+CD119+。在体外实验中，我们观察到重组IFN-α2b对NG亚群的数量、表型及吞噬活性有正向调节作用。结论。重组IFN-α2b在体外实验中表现出积极作用;因此，它可以被认为是未来中度COVID-19的潜在治疗工具。恢复I型IFN可能是COVID-19的有效治疗选择，因为它可以促进更快的病毒消除，恢复IFN系统的正常功能，并对NG亚群的表型具有积极的调节作用。关键词:中性粒细胞，亚群，COVID-19，表型，重组干扰素α2b

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来源期刊

Infektsionnye Bolezni Medicine-Infectious Diseases

CiteScore

1.30

自引率

0.00%

发文量

期刊介绍： The journal publishes original research works, reviews of literature, lectures, methodological recommendations, clinical observations. Main topics: problems of etiology, pathogenesis, clinical manifestations of infectious diseases, new techniques and methods of their diagnosis, prevention and treatment; special attention is paid to the problems of antibacterial and antiviral therapy, the use of immunoglobulins and interferons, and also to intensive therapy of critical states. The journal is in the List of leading scientific journals and periodicals of the Supreme Attestation Committee, where the principal results of doctoral dissertations should be published.