[Justifying genetic and immune markers of efficiency and sensitivity under combined exposure to risk factors in mining industry workers].

The authors evaluated and justified immunologic and genetic markers under combined exposure to risk factors in mining industry workers. Analysis covered polymorphism features of 29 genes with variant alleles possibly participating in occupationally conditioned diseases formation and serving as sensitivity markers of these diseases risk. The genes association selected demonstrates reliably changed polymorphism vs. the reference group (SOD2 superoxidedismutase gene, ANKK1 dophamine receptor gene, SULT1A1 sulphtransaminase gene, MTHFR methylene tetrahydrofolate reductase gene, VEGF endothelial growth factor gene, TNF-alpha tumor necrosis factor gene). Under combined exposure to occupational hazards (sylvinite dust, noise) in mining industry, this association can serve as adequate marking complex of sensitivity to development of occupationally conditioned diseases. Increased-production of immune cytokine regulation markers: tumor necrosis factor and vascular endothelial growth factor. Genes SOD2, ANKK1, SULT1A1, VEGF, TNFalpha are recommended as sensitivity markers, and the coded cytokines (tumor necrosis factor and endothelial growth factor) are proposed as effect markers in evaluation of health risk for workers in mining industry.

[Effect of opioid peptides on oxygen-dependent microbicidity of peripheral blood neutrophils].

Investigation ofopioid peptide effect on the production of reactive oxygen species by neutrophils in non-fractionated leukocyte suspension and in purified fraction of peripheral blood neutrophils is disclosed in this work. It was determined that selective delta- and micro-agonists of peptide origin stimulated the spontaneous and suppressed 15 mkg/ml zymosan-induced LDCL (luminol-dependent chemiluminescence) reaction of neutrophils in leukocyte suspension. beta-endorphin was found to render less marked suppressive action on 15 mkg/ml zymosan-induced LDCL, and delta2-agonist deltorphin 2 promoted 15 mkg/ml zymosan-induced LDCL only toward the 25 minutes of the experiment. beta-endorphin and selective d- and m- agonists did not affect the spontaneous and suppressed 15 mkg/ml and 150 mkg/ml zymosan-induced neutrophil LDCL. Therefore, opioid peptides play essential role in the process of direct and indirect regulation of oxygen-dependent system of neutrophil granulocyte bactericidal activity.

[Influence of polyoxidonium on IL-1 beta, TNF-alpha and IL-6 production by mononuclears and monocytes under the dexamethasone effect].

It was established that in a mononuclear fraction polyoxidonium inhibited the TNF-alpha production and stimulated the IL-1 beta and IL-6 production. In LPS-induced mononuclear cultures polyoxidonium inhibited the IL-6 production and had no statistically significant effect on the synthesis of TNF-alpha and IL-1 beta. Polyoxidonium had no effect on TNF-alpha, IL-6 and IL-1 beta production by purified monocytes. The addition of polyoxidonium with dexamethasone to the cultures only in monocyte fraction enhanced the IL-1 beta production as compared with the effect of dexamethasone alone. Data obtained allow suggesting that under certain conditions polyoxidonium could alleviate pronounced suppressive influence of glucocorticoids on a secretory activity of effectors of innate immunity.

Regulation of interleukin-1beta and interleukin-8 production by agonists of mu and delta opiate receptors in vitro.

The studies reported here showed that beta-endorphin at concentrations of 10(-7)-10(-11) M increased interleukin-1beta (IL-1beta) production in unfractionated leukocyte suspensions both in the presence of 0.1 microg/ml lipopolysaccharide (LPS) and in cultures not stimulated with LPS. Interleukin-8 (IL-8) production by leukocytes was inhibited by beta-endorphin at concentrations of 10(-7) and 10(-11) M in the presence of LPS. The stimulatory effect of beta-endorphin on IL-1beta production was not blocked by naloxone or naltrindole. Suppression of IL-8 production was blocked by naloxone and naltrindole. In the mononuclear cell and neutrophil fractions, beta-endorphin and the delta agonist DADLE increased IL-1beta synthesis in both the spontaneous and stimulated versions of the test, while beta-endorphin and the delta agonist DADLE inhibited IL-8 production in the mononuclear cell and neutrophil fractions only in LPS-stimulated cultures. The mu agonist DAGO had no effect on IL-1beta production by mononuclear cells or neutrophils, though it suppressed LPS-induced secretion of IL-8 by neutrophils.

[Regulation of IL-1beta and IL-8 production by mu-, delta-opiate receptors agonists in vitro].

The beta-endorphin 10(-7-)-10(-11) M in LPS (lypopolisaccharide) presence and in spontaneous cultures promoted the IL-1beta production in mixed leukocyte fraction. LPS-induced IL-8 production in leukocyte fraction was inhibited by beta-endorphin 10(-7), 10(-11) M. The enchasing effect of beta-endorphin on IL-1beta production was not blocked by naloxone and naltrindole. The inhibitory effect of beta-endorphin on IL-8 production was blocked by naloxone and naltrindole. In mononuclear and neutrophile fractions beta-endorphin and delta-agonist DADLE enchased IL-1beta production in spontaneous and LPS-stimulating cultures, when IL-8 production inhibited beta-endorphin and delta-agonist DADLE only in LPS presence. No effect of mu-agonist DAGO were observed on IL-1beta production, whereas LPS-induced IL-8 secretion in neutrophile fraction inhibited by DAGO.

Evaluation of the effect of beta-endorphin on IL-4 and gamma-IFN production by CD4+ lymphocytes.

Beta-endorphin stimulates phytohemagglutinin-induced production of IL-4 and does not modify the production of gamma-IFN in nonfractionated leukocyte suspension. In a culture of purified CD4+ T-cells, beta-endorphin does not modify the levels of IL-4 and gamma-IFN, but stimulates the production of IL-4 and inhibits gamma-IFN production after addition of monocytes to CD4+ lymphocytes. Stimulation of IL-4 synthesis by beta-endorphin is mediated by the cycloxygenase cycle products. Hence, beta-endorphin shifts T-helper polarization towards Th2 cells with subsequent predominance of the humoral form of the immune response.

Role of beta-endorphin in the regulation of proinflammatory cytokine production by peripheral blood monocytes in vitro.

beta-Endorphin activated interleukin-1beta production in the culture of unfractionated cells with lipopolysaccharide, but had no effect on the synthesis of tumor necrosis factor-alpha and interleukin-6. This peptide produced a slight stimulatory effect on spontaneous production of interleukin-1beta by cultured leukocytes. Opioid receptor blockade with naloxone and naltrindole did not abolish the stimulatory effect of beta-endorphin on interleukin-1beta production. beta-Endorphin did not modulate the synthesis of interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 in a purified fraction of monocytes.