Aim. To study the characteristics of interleukin-6 (IL-6), interleukin-1β(IL-1β), interferon-γ(INF-γ) secretion in rheumatic patients with and without anemia of chronic diseases. To assess the influence of these cytokines on the development of anemia of chronic iseases in patients with various rheumatic pathologies. To propose a working version of the classification of anemia of chronic diseases based on the leading pathogenetic factor in the development of anemia. Material and methods. 126 rheumatic patients, 34 men (45,8 (36–54,9) years old), 92 women (49,5 (38–60) years old) were examined. Group 1 included 41 patients with ACD, 34 with iron deficiency anemia (IDA). Group 2 had 29 patients with a combination of ACD and IDA, 22 in the control group without anemia. Comparative analysis between groups with and without anemia and correlation analysis of hemogram parameters, iron metabolism, C-reactive protein (CRP), interleukin-6 (IL-6), IL-1β, interferon gamma (INF-γ) were performed. Results. In the ACD group, the concentrations of ferritin, CRP, IL-6 were increased in comparison with other groups. With regard to IL-1β, INF-γ, no intergroup differences were found in the study groups (p>0,05). It was found that the greatest influence on the maturation of erythrocytes is exerted by INF-γ (r=-0,4). The greatest effect on hemoglobin synthesis is exerted by IL-6 (r=-0,6) and IL-1β (r=-0,4). The effect of the studied cytokines on erythropoiesis and hemoglobin synthesis can be realized through their effect on iron metabolism. This is confirmed by the results of the performed correlation analysis. A negative moderate correlation was shown between IL-6 and iron (r=-0,6), total iron binding capacity (TIBС)(r=-0,3), transferrin saturation index (TSI) (r=-0,5), ferritin (r=-0,5), transferrin (r=-0,3), and a moderately positive correlation with CRP (r=0,5). For INF-γ, a negative correlation was found with TIBC (r=-0,3), ferritin and transferrin (r=-0,3). For IL-1β, a moderate negative correlation was shown with TIBC, ferritin and transferrin (r=-0,4). Conclusion. It was found that patients with rheumatic pathology and anemia of chronic diseases had high concentration of IL-6, while the concentrations of INF-γ and IL-1β did not differ from the values in the groups of patients with IDA, a combination of AChD / IDA and without anemia. Despite this, the influence of all three investigated cytokines on erythropoiesis, hemoglobin synthesis and iron metabolism has been proven. The data obtained reflect the complex pathogenesis of ACD in patients with rheumatic pathology, including erythropoiesis disorders, changes in iron metabolism, and increased synthesis of some pro-inflammatory cytokines. A working version of the classification of ACD (with a predominant iron deficiency, with violations of the regulatory mechanisms of erythropoiesis, with insufficient production of erythropoietin) has been proposed.

The features of erythropoietin secretion in patients with a rheumatic pathology and anemia of the chronic diseases in comparison with patients having iron deficiency anemia, as well as the relationship between erythropoietin, hepcidin, proinflammatory, and antiinflammatory cytokines, have been investigated. 126 patients suffering from the rheumatic pathology were examined, including 34 men aged 3655 years and 92 women aged 3860 years. At the same time, 104 (82.5%) patients suffered from anemia, 22 (17.5%) patients did not have it. Patients suffering from anemia, depending on the leading pathogenetic factor, were divided into three groups such as: the 1st group patients suffering from anemia of chronic diseases; 2nd grouppatients suffering from a combination of anemia of chronic diseases and iron deficiency anemia; 3rd grouppatients suffering from iron deficiency anemia. In patients suffering from anemia of chronic diseases, the maximum concentration of interleukin-6, hepcidin, and the minimum concentration of erythropoietin were detected in comparison with the patients suffering from iron deficiency anemia and patients suffering from anemia of chronic diseases, and iron deficiency anemia (p 0.05). The maximum concentration of the erythropoietin has been established in patients suffering from iron deficiency anemia. About the concentrations of interleukin-10 and interleukin-1, tumor necrosis factor-, interferon-, no differences were found in the study groups. A direct correlation was found between the erythropoietin and erythrocytes (r = 0.57), hemoglobin (r = 0.41), hepcidin (r = 0.65). There was a strong negative correlation between the erythropoietin and interleukin-6 (r = 0.75), and a weak relationship with interferon gamma, tumor necrosis factor alpha, interleukin-10, and interleukin-1 (r 0.3). Thus, for patients with a rheumatic profile, a specific molecular profile should be identified, leading to the development of anemia of the chronic diseases, which consists in increased concentrations of hepcidin and interleukin-6 in combination with the insufficient secretion of erythropoietin. The found changes fit into the structure of the previously proposed working version of the classification of anemia of chronic diseases (with a predominant iron deficiency, with disturbances in the regulatory mechanisms of the erythropoiesis, with an insufficient production of erythropoietin). Isolation of the leading factor in the development of anemia of chronic diseases in the future will allow for a more optimal approach to its correction, including with the targeted therapy drugs.

Background:Anemia is widespread in rheumatic patients and is an important extra-articular manifestation that correlates with physical disability and increased mortality. The pathogenesis of such anemia is complex and multifactorial, including due to the influence of pro-inflammatory cytokines.Objectives:Our aim was to study the characteristics of the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) with anemia of chronic diseases (ACD), iron deficiency anemia (IDA) and a combination of ACD / IDA, as well as to study the effect of these cytokines on the development of anemia.Methods:There were examined 69 (54 (7 men /47 women, 50.6 ± 4.1 years) with anemia, 15 (6 men/9 women, 53.5 ± 2.74 years) without anemia) of RA patients. According to the criteria of Van Santen and Worwood, by determining the transferrin saturation index (TSI), ferritin, C-reactive protein (CRP), patients were divided into 4 groups: group 1 - ACD, 22 (5/17) patients (hemoglobin 79 [IQR, 95.6-111], red blood cells 3.5 [IQR, 3.6-4], TSI 25 [IQR, 14.7-26.2], ferritin 326.2 [IQR, 197.8-451.7], CRP 63.7 [IQR, 10.2-104.8]), group 2 - ACD / IDA, 18 (0/18) patients (hemoglobin 101 [IQR, 94-114], red blood cells 3.9 [IQR, 4-4.4], TSI 12.5 [IQR, 7.7-15], ferritin 50.1 [IQR, 11.9-74.9], CRP 45.8 [IQR, 17.6-54.9]), group 3 - IDA, 14 (2/12) patients (hemoglobin 108 [IQR, 100-115], red blood cells 4.5 [IQR, 4.1-4.9], TSI 9.7 [IQR 3-14], ferritin 21.8 [IQR, 7.2-28.9], CRP 8.6 [IQR, 2.7-8.6]), group 4 (control) - 15 patients without anemia (hemoglobin 141.4 [IQR, 133-147], red blood cells 4.6 [IQR, 4.3-4.9], TSI 23.1 [IQR, 16.6-27.8], ferritin 78.5 [IQR, 36-90.7], CRP 4.6 [IQR, 1.2-5.8]). The diagnosis of rheumatoid arthritis was made based on the 2010 ACR/EULAR classification criteria. The number of red blood cells and hemoglobin levels were determined on a Sysmex XS-500i analyzer (Japan). Concentrations of ferritin, CRP, TSI were determined on an Olympus Au 480 analyzer (Beckman Coulter, USA). Concentrations of IL-6, IL-10, and TNF-α were determined using a Stat Fax 2100 analyzer (Awareness Technology Inc., USA). The significance of differences between several unrelated groups was determined using the Kruskal-Wallis test at a significance level (p) of less than 0.05. To assess the relationship between the variables, the Spearman correlation coefficient (r) was calculatedResults:In the ACD group, there were the highest concentrations of CRP, ferritin in comparison with the other groups (p <0.05). TSI in the ACD group was higher compared with the IDA and ACD / IDA groups (p <0.05) and did not differ from the control group (p> 0.05). The maximum concentration of IL-6 was found in the ACD group (36.2 [IQR, 6.7-41]) compared with the ACD / IDA group (21.7 [IQR, 7.2-20.4]) (p <0, 05) and the IDA group (5.9 [IQR, 1.5-3.7]) (p <0.05) and without anemia (2.7 [IQR, 1.5-3) (p <0.05). Regarding IL-10 and TNF-α, no intergroup differences were found. A moderate correlation was found between the number of red blood cells and the concentration of IL-6 (r = -0.3), IL-10 (r = -0.4), TNF-α (r = -0.3). The relationship between the concentration of hemoglobin and IL-6 (r = -0.6), IL-10 (r = -0.4), TNF-α (r = -0.3) was revealed.Conclusion:In RA patients, IDA, ACD, as well as their combination, may occur. It is very important to clarify the genesis of anemia. ACD should be isolated separately because it has a complex pathogenesis, one of the important components of which are cytokines and their effect on erythropoiesis. The increased concentration of IL-6 in the group of patients with ACD, as well as the presence of a correlation between IL-6, red blood cells and hemoglobin, indicate the importance of this cytokine in the development of anemia. An increase in the concentration of ferritin and CRP also reflects the inflammatory genesis of anemia in patients with this anemia. The presence of a correlation between IL-10, TNF-α and hemogram indices suggests their influence on the development of anemia.Disclosure of Interests:None declared