The study of the immune status markers and characteristics of genetic polymorphism in potash mining workers under the impact of combined industrial factors was performed. We showed the inhibition ofphagocytosis and production of serum IgG and IgM, the deficiency of mediators of the immune and endothelial regulation of interleukin-17, VEGF, GAD1 and GAS6. The revealed changes are associated with the negative genetic fixation of key polymorphisms responsible as well for the detoxification of the first and second phase of the neuro-immune regulation, the state of the vascular endothelium and apoptosis, as both due to heterozygous and due to the homozygous variant genotypes of genes of cytochrome (CYP1A1), Sulfotransferase (SULT1A1), toll-like receptor (TLR4), tumor necrosis factor (TNF), endothelial growth factor (VEGFA)
The studies in the organism adaptation for the conditions of technogenic environmental changes, especially in child population, will allow to design a set of diagnostic markers for assessing the health status and early detection of pathological trends for development of hypersensitivity to environmental substances and improve efficiency of therapeutic and preventive measures. Metals are capable to alter functional activity of immune system by producing both immunostimulating and suppressive effects on immune reactivity, dependent on the properties of the given metal, its environmental concentration, source and duration of exposure. The aim of the present study was to investigate the features of hypersensitivity markers in children under the conditions of external exposure to aluminum. We have conducted a survey of the schoolchildren aged from 7 to 11 y.o. (a mean of 8.82±0.11 years), permanently inhabiting the territory of active industrial exposure associated with environmental contamination with aluminum compounds. The comparison group consisted of children from a “conventionally clean” area, with acceptable parameters of environmental quality. Specific features of sensitization developing to aluminum were evaluated, including both reactive and alternative mediator mechanisms (leukotrienes and prostaglandins), as well as participation of the cytokines in evolving sensitivity to the metal in the ex vivo experiments. We have shown a 1.43-fold increased level of metal in peripheral blood of the observation group, than in comparison group (respectively, observation group, 0.020±0.005 μg/ml; comparison group 0.014±0.003 μg/ml). Enhanced levels of IgE antibodies were found to be 2.13-fold higher compared to the reference values (213.55±88.10 IU/ml against normal rates of < 100.0 IU/ml) accompanied by increased specific IgG antibodies to aluminum (1.55-fold relative to the controls, i.e., 0.157±0.054 cu in observation group versus 0.101±0.041 cu for the comparison group), as well as a 2.09-fold increased spontaneous production of leukotrienes C4/D4/E4 (80.60±19.44 pg/ml for observation group; 38.51±2.40 pg/ml in the comparison group), which was 1.67-fold enhanced by experimental aluminum stimulation. Prostaglandin F2α levels among the children from observation group were increased 1.9-fold (observation group, 892.62±97.20 pg/ml; comparison group, 457.11±132.99 pg/ml, p < 0.05). Under the ex vivo experimental conditions, we observed mostly suppressive effects of aluminum upon the cytokine production. E.g., IL-4 production was inhibited by 2.13-fold, as compared with control values (observation group, 0.64±0.23 pg/ml; comparison group, 1.36±0.09 pg/ml); the suppression for IL-17 was 1.90 times (observation group, 1.08±0.27 pg/ ml; comparison group, 2.05±0.37 pg/ml, p < 0.05). The parameters studied may be used as aluminum hypersensitivity markers and used for monitoring and predictions in public health care.
Evaluation of the immune system parameters can be used in order to assess capacity to adapt under conditions of increased external chemical load, including exposure to metals, which can exert either activating and inhibitory effects upon immune regulation parameters. The aim of this work was the analysis of immunoregulatory markers in a children’s population who consumed water with high strontium content (a sample from the Perm region). We carried out immunological evaluation of the children aged 7 to 12 years, living at a territory with a high strontium content in the drinking water. The comparison group included children from the conventionally clean region. We studied differential changes in cellular immunity (phagocytosis rates), humoral factors of immune defense (serum immunoglobulins), development of specific sensitization for strontium, as well as the processes of apoptosis triggering and regulation. A 3.68-fold increase in strontium levels was shown in fresh water within observation area, and the average blood strontium content in the children of appropriate observation group was 1.55-fold higher than in children of the comparison group. At the same time, 1.2-fold increase in phagocytic activity determined as phagocytic number and phagocytic index was found, as compared to the control group. In 80% of the subjects, a reduction in serum IgG level was observed when compared to physiological norm, as well as a significant decrease in IgG and enhance in IgM production against the levels found in the comparison group. Wehave also shown an enhanced total sensitization in 55.0% of the observation group as shown by the total IgE test compared with normal age ranges, as well as excessive specific sensitization to strontium by 2.49 times, according to the IgG criterion. Disturbance in apoptosis triggering was associated with decreased number of CD95+ lymphocytes and TNFR1+ cells (2.8-fold compared to reference values), shifted balance in apoptogenic proteins, an average of 2.6-fold decrease in Bcl-2 expression, a 2.8-fold reduction of the p53 transcription factor expression relative to the reference interval. Thus, we have shown an ability of strontium excess in drinking water to influence the most important indices of immune regulation in pediatric population. These changes may serve as indices of populational health status under of external strontium exposure.
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