COMPARATIVE ANALYSIS OF THE SECRETION OF INTERLEUKIN-6, INTERLEUKIN-1BETA, INTERLEUKIN-10, TUMOR NECROSIS FACTOR-ALPHA, INTERFERON-GAMMA IN VARIOUS TYPES OF ANEMIA IN PATIENTS WITH HIV INFECTION

Abstract

Aim. To compare the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1-beta, tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) in patients with HIV infection with anemia of chronic disease (ACD), iron deficiency anemia (IDA), as well as their combination. To assess the effect of the studied cytokines on erythropoiesis in each of the studied types of anemia in this category of patients. Material and methods. 125 patients with HIV infection were examined: 101 with anemia (55 men, 46 women, 39.4±9.6 years), 24 patients with HIV infection without anemia (13 men, 11 women, mean age 37.6± 7.37 years). In accordance with the Van Santen and Worwood criteria, by determining the transferrin saturation index (TSI), ferritin concentrations, C-reactive protein (CRP), patients with anemia were divided into 3 groups: group 1 – 36 patients with ACD (19 men, 17 women, mean age 41.7±11.8 years), group 2 – 30 patients with a combination of ACD/IDA (18 men, 12 women, mean age 41.2±10 years), group 3 – 35 patients with IDA (18 men, 17 women, mean age 35.4±7.1 years). In all patients, the number of erythrocytes, the concentration of hemoglobin, ferritin, CRP, CNT, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-1beta (IL-1β), interferon-gamma (INF-γ). For quantitative indicators, the arithmetic mean, standard error of the mean, and interquartile range (IQR) were calculated. Significance of differences between several unrelated groups was determined using the Kruskal-Wallis’s test. To assess the relationship between variables, the Spearman correlation coefficient I was calculated. Results. In the ACD group, the maximum concentration of IL-6 (36.6 [IQR, 11.5-51.1]) and IL-10 (21.6 [IQR, 11.4-28.8]) compared with the ACD/IDA group (IL-6 (9.1 [IQR, 5.1-11.4]), IL-10 (15.5 [IQR, (7.1-21.6)]), and IDA (IL- 6 (6.2 [IQR, 1.6–7.2]), IL-10 (8.6 [IQR, 3.9–9.3]) (p<0.05). In the groups of patients with ACD and ACD/IDA, the maximum and almost equal concentrations of TNF-α (15.2 [IQR,6.1-24.1] in the ACD group and 17.3[IQR,7.9-17.3] in the ACD/IDA group), IL-1β (16.7[IQR,4.7-28.9] in the ACD group and 19.2 [IQR,3.9-28.8] in the ACD/IDA group), INF-γ ( 62.6[IQR,4.6-85.3] in the ACD group and 58.3[IQR,8.5-37.5] in the ACD/IDA group), which were statistically significantly higher than the concentrations of these cytokines in patients with IDA and the control group. There were no significant differences in the concentrations of TNF-α, IL-1β, IL-10 and IFN-γ between patients with IDA and the control group. Significant moderate and strong negative correlations were found in the groups of patients with ACD and ACD/IDA between all studied cytokines, erythrocytes and hemoglobin. In the IDA group, the correlation coefficients between cytokines, erythrocytes, and hemoglobin are low or absent. Conclusions. In patients with HIV infection, a wide prevalence of ACD has been shown, especially in patients with immunodeficiency and in the late stages of the disease. ACD, unlike IDA, has a complex multicomponent pathogenesis. This study shows the importance of pro-inflammatory and inflammatory cytokines in the development of ACD in HIV patients, including due to their negative effect on erythropoiesis and hemoglobin synthesis. A working version of the classification of ACD (with a predominant iron deficiency, with impaired regulatory mechanisms of erythropoiesis, with insufficient production of erythropoietin) has been proposed. It is necessary to further study the pathogenesis of ACD in this category of patients to improve treatment.