Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;71(3):331-341.
doi: 10.1007/s00011-022-01543-9. Epub 2022 Feb 14.

Cytokine producing ability of peripheral blood cells from COVID-19 patients after unspecific in vitro stimulation

Snezana Zivancevic-Simonovic  1 , Danijela Jovanovic  2   3 , Vojislav Cupurdija  2   3 , Olivera Milosevic-Djordjevic  4 , Marijana Stanojevic  3   5 , Milos Marinkovic  3 , Nebojsa Igrutinovic  3 , Ivan Stanojevic  6 , Danilo Vojvodic  6 , Olgica Mihaljevic  7
Affiliations

Cytokine producing ability of peripheral blood cells from COVID-19 patients after unspecific in vitro stimulation

Snezana Zivancevic-Simonovic et al. Inflamm Res. 2022 Mar.

Abstract

Objective and design: Perturbations of peripheral T cell homeostasis and dysregulation of the immune response to SARS-CoV-2, especially in severely ill patients, were observed. The aim of this study was to analyze the cytokine producing ability of peripheral blood cells from severely ill COVID-19 patients upon non-specific in vitro stimulation with phytohemagglutinin (PHA). Possible associations of cytokine levels with patients' age and gender, glucocorticosteroid therapy, as well as the trend of the inflammatory process at the time of sampling (increased or decreased) were also analyzed.

Subjects and methods: The study included 23 COVID-19 patients and 17 healthy control subjects. The concentrations of selected Th1/Th2/Th9/Th17/Th22 cytokines were determined using a multi-analyte flow assay kit.

Results: Our results showed that peripheral blood cells from severely ill COVID-19 patients had a much reduced ability to produce cytokines in comparison to healthy controls. When inflammation was raised, blood cells produced more IL-6 and IL-17, which led to increases of some Th17/Th1 and Th17/Th2 ratios, skewing towards the Th17 type of response. The methylprednisolone used in the treatment of patients with COVID-19 influences the production of several cytokines in dose dependent manner.

Conclusion: Our results indicate that the stage of the inflammatory process at the time of sampling and the dose of the applied glucocorticosteroid therapy might influence cytokine producing ability upon non-specific stimulation of T cells in vitro.

Keywords: COVID-19; Cytokine; Glucocorticosteroid; In vitro; Inflammation; Phytohemagglutinin.

PubMed Disclaimer

Conflict of interest statement

The authors stated that there are no conflicts of interest regarding the publication of this article.

Figures

Fig. 1
Fig. 1
Cytokine concentrations in PHA-stimulated whole blood cell cultures of COVID-19 patients analyzed in relation to gender (a) and age (b) and control subjects analyzed in relation to gender (c) and age (d)
Fig. 2
Fig. 2
Cytokine production from PHA-stimulated peripheral blood cells of COVID-19 patients in whom inflammation increased (n = 7) or decreased (n = 16). Significant differences in IL-17A (p = 0.015); significant difference in IL-6 (p = 0.026)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323:1239–1242. doi: 10.1001/jama.2020.2648. - DOI - PubMed
    1. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect. 2020;80:607–613. doi: 10.1016/j.jinf.2020.03.037. - DOI - PMC - PubMed
    1. Pat J, Alkan SS. How does SARS-CoV-2 manipulates the immune system? Critical role of Th1, Th2, Th17 responses. Turk J Immunol. 2020;8(2):100–102. doi: 10.25002/tji.2020.1270. - DOI
    1. Matic S, Popovic S, Djurdjevic P, Todorovic D, Djordjevic N, Mijailovic Z, Sazdanovic P, Milovanovic D, Zecevic DR, Petrovic M, Sazdanovic M, Zornic N, Vukicevic V, Petrovic I, Matic S, Baskic D. SARS-CoV-2 infection induces mixed M1/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets. PLoS ONE. 2020;15(12):e0241097. doi: 10.1371/journal.pone.0241097. - DOI - PMC - PubMed
    1. Ahmed SF, Quadeer AA, McKay MR. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses. 2020;12(3):254–273. doi: 10.3390/v12030254. - DOI - PMC - PubMed