Controversial role of neutrophilic granulocytes in the immunopathogenesis of COVID-19: correlation with imbalance of pro-inflammatory neutrophil-associated cytokines and interferon alpha deficiency.
Infektsionnye Bolezni
; 20(4):12-24, 2022.
Article
in Russian
| EMBASE | ID: covidwho-2317647
ABSTRACT
Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
covid-19; cytokines; interferons; net; neutrophilic granulocytes; phenotype; recombinant IFNalpha-2b; subsets; adult; apoptosis; article; controlled study; coronavirus disease 2019; cytotoxicity; enzyme activity; enzyme linked immunosorbent assay; flow cytometer; gene expression; homeostasis; human; human cell; immunopathogenesis; inflammation; neutrophil; neutrophil extracellular trap; alpha2b interferon; antioxidant; CD16 antigen; CD63 antigen; cytokine; endogenous compound; gamma interferon; immunoglobulin enhancer binding protein; interferon; interleukin 17; interleukin 18; interleukin 1beta; interleukin 6; interleukin 8; reduced nicotinamide adenine dinucleotide phosphate oxidase; tumor necrosis factor; vasculotropin A
Full text:
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
Russian
Journal:
Infektsionnye Bolezni
Year:
2022
Document Type:
Article
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