Abstract

Today, increasing attention is being paid to the role of circadian rhythms in pathology. There are time-of-day-dependent immune markers that provide valuable information about disease progression. The aim of this study was to measure evening and morning concentrations of a few cytokines (interleukins, adhesion molecules, tumor necrosis/growth factors, etc.) in the peripheral blood of patients with stage II essential hypertension and to investigate how they correlate with a nocturnal blood pressure decline. Blood samples were collected from 90 patients with stage II EH at 7:00 a.m. and 8:00 p.m. Cytokine concentrations were measured using immunoassays. Based on 24-h blood pressure monitoring, the patients were distributed into 3 groups: dippers, non-dippers and night-peakers. The morning to evening ratios of cytokine concentrations in patients with EH differed from those in healthy controls due to an increase in the evening concentrations of somnogenic cytokines (IL1β, IL1α) and LIF, sLIFr, and M-CSF whose daily fluctuations patterns remain understudied. On the whole, the fluctuation patterns of the measured cytokines in patients with stage II EH who had had the condition for 10 to 14 years and were receiving no antihypertensive treatment at the time of our study differed from those displayed by healthy controls. A twenty percent rise in the evening concentrations of IL1α, LIF, sLIFr, M-CSF, and erythropoietin contributes significantly to pathological blood pressure rhythms (as demonstrated by the groups of non-dippers and night-peakers) in patients with stage II EH receiving no antihypertensive therapy. Understanding the pathophysiological role of cytokine levels and their fluctuations over a 24-h cycle could inspire new methods for EH prevention and reduce end-organ damage.

Highlights

  • Author contribution: Radaeva OA recruited the study participants, collected blood samples, interpreted the results, analyzed the literature, and helped to write a draft of the manuscript

  • The patients with stage II essential hypertension (EH) who had been suffering from this condition for 10 to 14 years and were not receiving antihypertensive therapy around the time of the study, had higher morning concentrations of IL1β, IL1α, IL18, IL18BP, IL6, sIL6r, LIF, TNFα, sTNF-RI, IL10, TGF-β1, IL8, CX3CL1, CXCL10, INFγ, M-CSF, and erythropoietin (р < 0.001) and lower morning concentrations of IL1ra (р < 0.001) than the healthy controls (Table 1)

  • The following dynamics were observed in the control group in the evening: IL1β levels rose by 14.1% (0.37), р < 0.05; IL1α, by 14.8% (0.33), р < 0.05; IL6, by 29.2% (0.98), р < 0.001; TNFα, by 12.3% (0.78), р < 0.01; sTNF-RI, by 12.6% (0.65), р < 0.05; IL1ra dropped by 14.6% (0.32), р < 0.01; IL10, by 23% (0.58), р < 0.01, and sIL6r, by 30.4% (1.54), р < 0.001

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Summary

Introduction

Author contribution: Radaeva OA recruited the study participants, collected blood samples, interpreted the results, analyzed the literature, and helped to write a draft of the manuscript. Compliance with ethical standards: the study was approved by the Ethics Committee of Ogariov Mordovian State University (Protocol 12 dated December 14, 2008). All patients gave their informed consent to participate. Целью исследования было изучить содержание цитокинов (интерлейкинов, молекул адгезии, факторов некроза опухоли, роста и др.) в сыворотке периферической крови больных эссенциальной артериальной гипертензией (ЭАГ) II стадии в утреннее/вечернее время и его корреляцию со степенью снижения артериального давления (АД) в ночное время. Повышение концентраций IL1α, LIF, sLIFr, M-CSF, эритропоэтина в 20.00 ч на 20% и более является значимым компонентом формирования патологических околосуточных ритмов АД («Non-dipper» и «Night-peaker») у больных ЭАГ II стадии при длительности заболевания 10–14 лет (без приема гипотензивных препаратов). В Ховряков: набор группы пациентов, забор материала для исследования, компьютерная работа с текстом

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