ORIGINAL RESEARCH

Altered circadian expression of cytokines in blood of patients with essential hypertension following COVID-19

About authors

1 National Research Mordovia State University, Saransk, Russia

2 State Research and Development Institute of High Purity Biologicals of the Federal Medical and Biological Agency, Saint-Petersburg, Russia

Correspondence should be addressed: Olga A. Radaeva
Ulyanova, d. 26a, Saransk, 430032, Russia; ur.liam@demaveadar

About paper

Funding: supported by the grant of the Russian Science Foundation ‘Analysis of altered circadian expression of cytokines in blood of patients with essential hypertension as predictor of cardiovascular complications’, № 23-25-00147.

Author contribution: Radaeva OA — trial design, analysis of results, preparation of a manuscript; Simbirtsev AS — stating the purpose of the trial, editing; Kostina YuA — lab research, preparation of a manuscript; Iskandyarova MS — working with literature, editing; Negodnova EV — working with literature, surveillance over patients; Mashnina SV, Krasnoglazova KA, Babushkin IO — statistical treatment of data; Eremeev VV — editing.

Compliance with ethical standards: The trial was approved by the Ethics Committee of the National Research Mordovia State University (protocol № 12 as of December 14, 2008, protocol № 85 as of May 27, 2020). All patients signed a voluntary informed consent form. Biological sample (blood) was obtained in accordance with the provisions of Declaration of Helsinki of BMA (2013), protocol of Council of Europe Convention for the Protection of Human Rights and Biomedicine (1999) and additional protocol to Convention for the Protection of Human Rights and Biomedicine in the area of biomedical research (2005).

Received: 2023-11-29 Accepted: 2023-12-14 Published online: 2023-12-31
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In spite of a vast number of trials devoted to quantitative characteristics of the cytokine profile in patients with various diseases, no exact reference intervals are presented. It is just as important that there is a limited number of trials analyzing circadian rhythms of cytokine synthesis in patients with arterial hypertension. The purpose of the work was to analyze the characteristics of circadian rhythms of cytokines (IL18, IL18 BP, LIF, sLIFr, M-CSF, MCSFR) in patients with Grade II essential arterial hypertension, and to detect pathogenetically significant characteristics developed following Covid-19. Blood samples were taken at 7.00–8.00, 12.00–13.00, 19.00–20.00.00, 00.00–1.00 to determine the levels of IL18, IL18 BP, LIF, sLIFr, M-CSF, MCSFR in 18 patients (56 (95% CI (54–69) years) with essential arterial hypertension (EAH) within three days prior to and following Covid-19. For this, the immunoenzyme method was used. The obtained data demonstrated altered circadian expression of cytokines in the peripheral blood of patients with essential hypertension depending on whether they have EAH or not, and their additional distortion following Covid-19, which is stable in the majority of cases. It is preserved for six months as low IL18 BP (р < 0.001), and twofold increase of sLIFr and MCSF (р < 0,001) at 18.00. A significant association is determined between the circadian rhythms of sLIFr and altered systolic BP resulting in the abnormal rhythm with BP rise at night (night peaker) in patients with EAH following COVID-19. The obtained fundamental data offer prospects for new research of immunopathogenesis following COVID-19 in patients with hypertension taking into account circadian rhythms of cytokines in the blood.

Keywords: essential hypertension, M-CSF, LIF, sLIFr, circadian rhythms

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