Дисбаланс цитокинов и численность неклассических моноцитов в крови при сердечной недостаточности ишемического генеза

Background. Chronic heart failure frequently occurs against the background of ischemic heart disease (IHD), and has also been associated with the diagnosis of ischemic cardiomyopathy (ICMP). While there are significant commonalities with respect to underlying mechanisms, it would be most important to identify differential diagnostic markers to facilitate diagnosis and verification at the early stages of disease. Aim. The intent of this study was to perform a quantitative assessment of non-classical monocytes in patients diagnosed with IHD with or without ICMP and to identify any relationships between non-classical monocytes and plasma concentrations of proinflammatory (interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines. Methods. We examined 44 patients diagnosed with IHD, aged 49 - 63 years, with class II-III heart failure as per the New York Heart Association criteria. Of this group, 18 were also diagnosed with ICMP. The comparison group included 14 age-matched healthy controls. Percentages of non-classical (CD14+CD16+) monocytes in peripheral blood were determined by flow cytometry and the concentrations of IL-1β, IL-4, IL-6, IL-10, IL-13 and TNF-α were measured by enzyme-linked immunosorbent assay. Results. Amongst the patients diagnosed with ICMP, the concentration of IL-10 in blood plasma was higher than in those without this diagnosis, detected at 30.05 pg/ml (range 24.75 - 33.50 pg/ml, р=0.0412); the percentage of non-classical monocytes was lower, at 5.05% (range 4.08 - 6.58%, р=0.0094). Amongst patients diagnosed with IHD without ICMP, these parameters were within normal limits. The plasma concentrations of IL-1β, IL-6 and IL-13 in both groups were comparable to values obtained from healthy donors and IL-4 was undetectable throughout. Amongst patients diagnosed with ICMP, plasma TNF-α was detected at elevated levels that were comparable to those determined for patients diagnosed with IHD without ICMP. Conclusion. Imbalance of cytokines in blood in patients with coronary artery disease is characterized by excess TNF-α, absence of IL-4, and normal levels of IL-1β, IL-6 and IL-13, regardless of the type of ischemic myocardial injury. In patients with ICMP, we detected an overall decrease in the fraction of non-classical monocytes in association with an increase in plasma IL-10; these features were not detected in patients diagnosed with IHD without ICMP. As such, these biological responses may be used for timely diagnosis of ICMP. Received 27 May 2019. Revised 7 October 2019. Accepted 30 October 2019. Funding: The work is supported by grants of the Russian Foundation for Basic Research No. 18-015-00160\19 and the President of the Russian Federation No. НШ-2690.2018.7 and No. МД-2788.2019.7. Conflict of interest: Authors declare no conflict of interest. Author contributions Conception and study design: V.M. Shipulin, S.P. Chumakova Data collection and analysis: V.M. Shipulin, S.P. Chumakova, O.I. Urazova, M.V. Vins, V.V. Novickiy Literature review: S.P. Chumakova, D.A. Pogonchenkova, A.S. Pryakhin Drafting the article: S.P. Chumakova, D.A. Pogonchenkova, O.I. Urazova Critical revision of the article: V.M. Shipulin, V.V. Novickiy Statistical analysis: S.P. Chumakova Final approval of the version to be published: V.M. Shipulin, S.P. Chumakova, D.A. Pogonchenkova, O.I. Urazova, M.V. Vins, A.S. Pryakhin, V.V. Novickiy