Interleukins 4 and 6 as factors of modulation of subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy

Abstract

Aim. To evaluate the ratio of the fractions of classical, intermediate, non-classical and transitional monocytes in correlation with the concentration of interleukins 4 and 6 in the blood of patients with ischemic cardiomyopathy. Methods. 18 patients with ischemic cardiomyopathy (17 men and 1 woman) aged 47-66 years with circulatory insufficiency of functional class II-III according to the classification of heart failure of the New York Heart Association, were examined. The control group included 14 healthy donors matched by gender and age to patients with ischemic cardiomyopathy without any diseases of cardiovascular system and other systems in an exacerbation stage. In blood of the patients with ischemic cardiomyopathy, the relative content of classical (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14+CD16+) and transitional (CD14+CD16-) monocytes was assessed by flow cytometry and the concentration of interleukins 4 and 6 by enzyme-linked immunosorbent assay (ELISA). Results. It was shown that the number of non-classical monocytes in the blood of patients with ischemic cardiomyopathy was 2 times lower than normal (5.05 % [4.08; 6.58] and 10.07 % [9.34; 13.84], respectively, p < 0.01), as well as the concentration of interleukin-4 (0.02 pg/ml [0; 0.04] and 0.15 pg/ml [0.05; 0.65], respectively, p < 0.05). The number of classical monocytes in the blood of patients had a tendency to decrease, and the proportion of intermediate monocytes and the concentration of interleukin-6, on the contrary, were slightly higher than in healthy individuals, and were interdependent (r = 0.61; p < 0.05). The relative content of transitional monocytes in the blood was comparable with that of healthy donors. Conclusions. The subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy is characterized by a deficiency of the fraction of non-classical monocytes with protective properties against endothelium, and interleukin-4 in the blood with a certain increase in the content of interleukin-6 and the number of intermediate cells with ability to cooperate with T-lymphocytes, which predisposes to diffuse atheromatosis of small coronary arteries and diffuse hypoxic myocardial damage in ischemic cardiomyopathy.

Characteristics of Humoral Regulation of Differentiation of Bone Marrow Monocyte Subpopulations in Patients with Ischemic Cardiomyopathy

“…(16) Therefore, it can be speculated that insufficient generation of these monocytes in atherosclerosis patients can predispose to an enhanced fixation of lipids to the endothelium of coronary microvessels and thereby contribute to the development of diffuse myocardial ischemia and ICMP. (14) In patients without ICMP, classical and intermediate monocytes were the most abundant in BM among studied subpopulations, while in patients with ICMP, transient monocytes were predominant (Fig.1). In both groups, a negative correlation between percentages of transitional and classical cells was observed (r=-0.69; P<0.01 and r=-0.72; P<0.01 in ICMP+ and ICMP-groups of patients, respectively).…”

“…The results obtained were in line with the previously described deficit of this monocyte subtype in CHD, and could indicate an impairment of non-classical monocyte generation in patients with CHD accompanied by ICMP. (14) Non-classical monocytes were shown to perform a scavenging function via elimination of dead cells, pathogens and oxidized lipids from vessel walls. (16) Therefore, it can be speculated that insufficient generation of these monocytes in atherosclerosis patients can predispose to an enhanced fixation of lipids to the endothelium of coronary microvessels and thereby contribute to the development of diffuse myocardial ischemia and ICMP.…”

“…(7,11) In contrast, ICMP is characterized by a deficit of non-classical monocytes in the blood, while the number of other monocyte subtypes remains unchanged. (14) This suggests that in ICMP patients, the process of monocyte differentiation in BM might have considerable differences compared to CHD patients without ICMP. Identification of patterns of humoral regulation of monocytopoiesis in ICMP will allow for further elucidation of the pathogenesis of this disease and, possibly, discovery of new treatment strategies.…”