Comparison of cytokine secretion and study of their effect on erythropoiesis in patients with malignant neoplasms with anemia of chronic disease, iron deficiency anemia, and their combination

Abstract

Aim. To compare the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in cancer patients with anemia of chronic disease (ACD), iron deficiency anemia (IDA) and a combination of these two anemia types. To assess the effect of the studied cytokines on erythropoiesis in patients with malignant neoplasms separately for each type of anemia studied.Materials and methods. 106 patients with stage II–IV of solid malignant neoplasms were examined: 84 with anemia (55 men, 29 women, 67.1 ± 9.9 years), 22 without anemia (17 men, 5 women, mean age 60.2 ± 14.9 years). In accordance with Van Santen and Worwood criteria, by determining the transferrin saturation coefficient, ferritin concentrations, C-reactive protein, patients were divided into 4 groups: group 1 – patients with ACD, 31 (20 / 11 patients), 2 group – ACD / IDA, 28 (18 / 10 patients), group 3 – IDA, 25 (17 / 8 patients), group 4 (control) – 22 patients without anemia. In all patients, the number of erythrocytes, the concentration of hemoglobin, ferritin, C-reactive protein, transferrin saturation coefficient, IL-6, TNF-α, IL-10 were determined. For quantitative indicators, the arithmetic mean and interquartile range (IQR) were calculated. Significance of differences between several unrelated groups was determined using the Kruskal–Wallis test. To assess the relationship between variables, the Spearman correlation coefficient (r) was calculated.Results. In the ACD group, the maximum IL-6 concentration was 73.3 (IQR 6.2–51), TNF-α – 24.4 (IQR 15.3–60.7) and IL-10 – 8.7 (IQR 4.7–12.1) compared with the ACH3 / IDA group (IL-6 – 9.3 [IQR 4.4–13.2], TNF-α – 7.2 [IQR 4.5–9.6] and IL-10 – 6.7 [IQR 4.1–11.4]), and the IDA group (IL-6 – 3.4 [IQR 1.4–5.9], TNF-α – 4.6 [IQR 3.7–6] and IL-10 – 2.5 [IQR 0–5]) (p <0.05). In the ACD group, the highest correlation coefficients were found between IL-6 and erythrocytes (r = –0.74) and hemoglobin (r = –0.88), between TNF-α and erythrocytes (r = –0.66) and hemoglobin (r = –0.77), between IL-10 and erythrocytes (r = –0.36) and hemoglobin (r = –0.63). In the IDA group, the correlation coefficients between cytokines, erythrocytes, and hemoglobin are low or absent.Conclusion. In cancer patients, ACD, IDA, as well as their combination can occur. Increased cytokine secretion in ACD group patients is important due to the proven strong negative effect of cytokines on erythropoiesis. Further study of ACD pathogenesis is needed in order to improve treatment.