A-research concept and design; B-collection and/or assembly of data; C-data analysis and interpretation; D-writing the article; E-critical revision of the article; F-final approval of the article Aim. To determine the pathogenetic role of hepcidin in the development of anemia of inflammation in young children. Materials and methods. The content of hepcidin, ferritin and erythropoietin was studied in young children. The serum total iron-binding capacity, the coefficient of saturation of iron in transferring was determined. The main group consisted of children with acute inflammatory bacterial diseases of the respiratory system: the first subgroup included children with anemia of inflammation, the second group-without anemia. The comparison group included children with iron deficiency anemia without inflammatory manifestations. The control group consisted of conditionally healthy children. The studied groups were age-and sex-representative. Results. Patients with acute bacterial diseases of respiratory tract who developed anemia of inflammation had an elevated level of hepcidin, doubling the control group indicator (2.09 (1.81; 2.24) ng/ml and 1.07 (0.98; 1.17) ng/ml, respectively, P < 0.05). Its increase did not depend on the etiological factor of the disease; however, it increased with the disease severity. Low iron content was found in the first subgroup compared with other groups (P < 0.05), and in the second subgroup, there was an increasing trend in its content (P > 0.05). A high level of ferritin was detected in both subgroups, the concentration of which was 2 times higher than in the control group (P < 0.05). A close direct correlation was established between the serum contents of hepcidin and ferritin in the studied groups of children (r = +0.93, P < 0.01). The coefficient of saturation of iron in transferring was lower in the main group than in the comparison and control groups (P < 0.05). The level of serum total iron-binding capacity was statistically significantly decreased in the first subgroup (P < 0.05), and significantly increased in the second subgroup (P < 0.05), while there was only its downward trend (P > 0.05) in the comparison group. An increase in the content of erythropoietin was observed only in the group of children who were diagnosed with iron deficiency anemia. Its level was statistically significantly higher than the indicators of both subgroups of the main and control groups (P < 0.01). Conclusions. Hepcidin plays a significant pathogenetic role in the development of anemia of inflammation in young children due to the regulatory effect on iron deposition. The increase in its level in response to the development of a bacterial inflammatory process of the respiratory system in young children did not depend on the etiological factor of the disease.
Aim. To determine the probable role of ferroptosis in the course of inflammatory bacterial diseases of the respiratory system in young children, accompanied by the development of anemia of inflammation. Materials and methods. The study included 62 children (mean age 1.4 ± 0.4 years). The main group included 42 children with acute inflammatory bacterial diseases of the respiratory system, accompanied by anemia of inflammation: 29 children were diagnosed with bacterial bronchitis, 13 children – pneumonia. Determination of the severity of inflammatory diseases was determined by Acute Bronchitis Severity Score and Pediatric Respiratory Severity Score. At the time of participation in the study, all patients under observation had no signs of impaired iron metabolism, including iron deficiency anemia, in the anamnesis. The control group included 20 relatively healthy children. The content of caspase-7, caspase-9, ferritin, nitrotyrosine, phospholipase A2 was determined by ELISA using commercial kits. Results. We hypothesized the ineffectiveness of apoptosis in the course of bacterial inflammatory processes of the respiratory organs in young children, accompanied by the development of anemia of inflammation, and studied the probability of ferroptosis in these conditions. The obtained data indicated the presence of active oxidative stress in the main group patients. The strong direct correlation between the severity of inflammatory disease and the intensity of oxidative stress was revealed (r = 0.7, P < 0.001). A statistically significant increase in ferritin content in the main group compared with the control group was observed. There was a strong direct correlation between ferritin levels and the severity of bronchitis (r = 0.82, P < 0.01) and the severity of pneumonia (r = 0.87, P < 0.01). It was found that the upper quartile of serum ferritin levels (73.2 ± 4.6 ng/ml) was associated with severe disease. We assumed that restriction of access to iron for bacterial pathogens due to its sequestration in cells is a pathological process under certain conditions. Conclusions. In the pathogenesis of bacterial inflammatory diseases of the respiratory organs in young children, accompanied by the development of anemia of inflammation, the processes of apoptosis did not dominate, but, obviously, necrotic phenomena did, including ferroptosis as one of the manifestations of necrosis. The protective mechanism aimed at limiting the access of bacterial pathogens to iron due to its sequestration in cells becomes pathological under certain conditions.
Background. The purpose was to study the pathophysiological relationship of vitamin D and interleukin-6 (IL-6) and its role in the development of anemia of inflammation in young children with acute inflammatory bacterial diseases of the respiratory tract. Materials and methods. The content of 25(OH)D3, IL-6, and ferritin was analyzed in 40 young children (average age 1.6 ± 0.4 years) by enzyme immunoassay. The basic group consisted of 20 children with acute inflammatory bacterial diseases of the respiratory tract: 14 patients were diagnosed with acute bacterial bronchitis, and 6 children were diagnosed with pneumonia. Patients of the basic group were divided into two subgroups: the first group consisted of 10 children with anemia of inflammation, the second — 10 children with acute bacterial diseases of the respiratory tract without manifestations of anemia. The comparison group consisted of 10 children with iron deficiency anemia without manifestations of inflammatory respiratory diseases. Ten apparently healthy children represented the control group. Results. In the first subgroup of children, the level of 25(OH)D3 was borderline (29.99 (28.1; 36.5) ng/ml), in the second subgroup, its insufficiency was observed (27.4 (26.1; 31.2) ng/ml). The level of 25(OH)D3 was 1.3–1.6 times lower than the indicators of patients in the control group (43.0 (38.2; 47.0) ng/ml) (p < 0.05). The level of 25(OH)D3 in the blood serum of children from the comparison group (38.0 (34.0; 41.0) ng/ml) did not differ from the data in the control group (p > 0.05), but compared to the basic group, it was significantly higher (p < 0.05). The analysis of the IL-6 content in the blood serum of children showed that in the first subgroup its level exceeded the values of the control group (5.63 (4.52; 5.74) pg/ml) (p < 0.05) but was statistically lower than the indices obtained in the second subgroup (6.63 (4.82; 8.93) pg/ml) (p < 0.05). At the same time, we did not find a statistically significant difference between the indices of the comparison and control groups (p > 0.05). When the level of vitamin D supply is below 30 ng/ml, the established relationships are violated and the deposition of iron worsens, which in turn creates conditions for the further vital activity of the pathogen. Conclusions. The course of acute inflammatory bacterial diseases of the respiratory system in young children is characterized by a decrease in the level of vitamin D3 in the blood serum whereby the content of pro-inflammatory cytokines negatively correlates with the level of vitamin D. The development of anemia of inflammation indicates a certain balance of pro- and anti-inflammatory factors in the pathogenesis of acute inflammatory bacterial diseases of the respiratory tract in young children.
Background. Randomization of pathogenetic factors that determine the risk of developing anemia of inflammation in young children with acute inflammatory bacterial diseases of the respiratory system, and the creation of a mathematical model for predicting its development were the purposes of the study. Materials and methods. The study groups included 80 children, the average age of the patients was 1.6 ± 0.3 years. The basic group consisted of 40 children with acute inflammatory bacterial respiratory diseases, which, taking into account the hematological picture, was divided into two subgroups: the first subgroup — 26 children with anemia of inflammation, which was determined 4–5 days after the onset of the disease; the second subgroup — 14 children without anemia. The comparison group enrolled 20 children with iron deficiency anemia without inflammatory manifestations. The control group consisted of 20 apparently healthy children. To identify the signs that are most associated with the development of anemia of inflammation, the method of factor analysis was used. The basis of modeling for the selection of factor complexes was the Spearman correlation matrix with the subsequent determination of the factor loading. The analysis of the prognostic significance of individual signs as risk factors for the development of anemia of inflammation in young children with acute inflammatory bacterial respiratory diseases was carried out based on calculating the relative risk (RR) index in 2 x 2 contingency tables with the determination of 95% confidence intervals (95% CI) and Pearson’s χ2 test. The most significant factors included informative signs with an RR value of more than 1.0. To predict the probability of developing anemia of inflammation, the method of binary logistic regression was used. Results. The factorial analysis results demonstrated five factors that have eigenvalues greater than 1.0 and describe 70.5 % of the total dispersion of the variables. Factor 1, the “factor of iron metabolism”, described 21.5 % of the total variance and included 2 variables: the number of red blood cells and the level of hepcidin. Factor 2, the “anemia factor”, described 14.6 % of the total dispersion and included hemoglobin levels. Factor 3, “oxidative stress factor”, described 12.7 % of the total dispersion and included 2 variables: nitrotyrosine content and IL-6 level. Factor 4, the “pro-inflammatory factor”, described 12.2 % of the total dispersion and included data on phospholipase A2 content and the severity of the inflammatory disease. Factor 5, “iron deposition factor”, described 8.9 % of the total dispersion and included ferritin level data. At the next stage, calculating the RR index, we identified five risk factors that have the greatest influence on the development of anemia of inflammation: ferritin content (≥ 73.2 ± 4.6 ng/ml), the presence of gram-negative microflora as a bacterial agent that caused the development of inflammatory diseases, the presence of febrile fever in the patient, repeated episode of inflammatory disease, hepcidin level (≥ 1.9 ± 0.11 ng/ml). Conclusions. Based on the results of the conducted factor analysis, a prognostic model was formed for the development of anemia of inflammation in young children with acute inflammatory bacterial respiratory diseases. According to the results of factor analysis, it was found that the leading contribution to the pathogenesis of the development of anemia of inflammation was made by disorders of iron metabolism against the background of the inflammatory process, including the processes of iron deposition; oxidative stress, and interleukin-6. It is advisable to use certain risk factors and the results of predictive modeling regarded to the group of high risk of developing anemia of inflammation in young children with acute inflammatory bacterial respiratory diseases.
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