MODELING OF COMBINED EFFECTS OF THE EXPOSURE TO CHEMICALS (ALUMINUM) AND REGULATORY IMMUNE AND ENDOCRINE FACTORS IN RESEARCH ON CYTOKINES PRODUCTION IN EXPERIMENTS IN VITRO

Introduction. Analysis of individual components of the network of regulatory neuroendocrine and immune interactions, as well as their possible combination with the use of mathematical modeling technology, makes it possible to identify the likely consequences of the negative impact of man-made environmental factors on public health and to determine optimal strategies for reducing morbidity. The aim of the work is to simulate cytokines production in vitro under the combined effect of chemical factors (aluminium) and regulatory immune and endocrine mediators. Material and methods. The experiment was performed on peripheral blood samples of healthy donors (n=68). An immune cell suspension was used, isolated by centrifugation in a ficoll-verografin density gradient. Viral load modeling was performed with a complex mitogen. The following factors were used: IL-1 β, cortisol, aluminum. The concentration of cytokines IL-8, IL-10, IL-17 was determined by enzyme immunoassay. Statistical analysis was performed using Statistica 6.0. Results. A significant change in the production of IL-8 and IL-10 was found in groups with different levels of experimental IL-1 exposure. The combined effect of IL-1 and high levels of cortisol and aluminum increased the levels of IL-8 and IL-10. In the study of the production of IL-17 inhibitory effects with increasing concentrations of IL-1 were revealed. The nonlinear equations of the concentrations dependences of the studied cytokines on the content of IL-1, cortisol and aluminum were determined with checking the models adequacy to the experimental data by the method of dispersion analysis. Discussion. The study of characteristics of the changes in immune cytokine mediators under the influence of physiological and chemical factors has revealed the interaction mechanism of a specific chemical environment and immune-endocrine regulation system components during the course of immunological processes in the body. Conclusion. The results of the study showed interrelations in the system of cytokine immune mediators associated with the increased production of IL-8 and IL-10 and a decrease in IL-17 under conditions of increasing concentrations of IL-1, as well as with the combined effect of cortisol and aluminum. Mathematical modeling has determined the nonlinear nature of the identified patterns.

Dolgih O.V., Krivtsov A.V., Bubnova O.A., Otavina E.A., Bezruchenko N.V., Kolegova A.A. et al. Features of fixing the genetic polymorphism in dyads “mother-child” in the conditions of aerogenous exposure to metals. Gigiena i sanitariya. 2017; 96(1): 26-9 (in Russian).

Dolgikh О.V., Krivtsov А.V., Starkova К.G., Luchnikova V.А., Bubnova О.А., Dianova D.G., Bezruchenko N.V., Vdovina N.A. Neurotransmitter system of immune regulation as a marker of immunological disorders in pupils in the conditions of increased entry of strontium with drinking water. Health Risk Analysis. 2015; 3: 61-7. DOI: 10.21668/health.risk/2015.3.09.eng

Lanin D.V., Zaitseva N.V., Dolgikh O.V. Neuroendocrine Mechanisms for Regulation of Immune System. Uspekhi sovremennoy biologii. 2011; 131(2): 122-34. (in Russian).

Lanin D.V. The analysis of the co-regulation between the immune and neuroendocrine systems under exposure to risk factors. Health Risk Analysis. 2013; 1: 73-81. DOI: 10.21668/health.risk/2013.1.10.eng

Duramad P., Holland N.T. Biomarkers of immunotoxicity for environmental and public health research. Int. J. Environ. Res. Public Health. 2011; 8(5): 1388-401.

Lanin D.V., Chigvintsev V.M. Features of the immune and neuroendocrine regulation in children living under conditions of aero exposure to phenol, methanol and formaldehyde. Rossiyskiy immunologicheskiy zhurnal. 2015; 9 (18), 2 (1): 76-8 (in Russian)

Trusov P.V., Zaitseva N.V., Kir’yanov D.A., Kamaltdinov M.R., Tsinker M.Yu., Chigvintsev V.M., Lanin D.V. A Mathematical Model for Evolution of Human Functional Disorders Influenced by Environment Factors. Matematicheskaya biologiya i bioinformatika. 2012; 7(2): 589-610. (in Russian).

Trusov P.V., Zaitseva N.V., Chigvintsev V.M., Lanin D.V. Mathematical model for describing antivirus immune response regulation allowing for functional disorders in a body. Health Risk Analysis. 2017; 4: 117-128. DOI: 10.21668/health.risk/2017.4.13.eng

Fouchet D., Regoes R. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells. PLoS ONE. 2008; 3(5): e2306.

Zaitseva N.V., Trusov P.V., Shur P.Z. et al. Methodical approaches to health risk assessмеnt of heterogeneous environmental factors based on evolutionary models. Health Risk Analysis. 2013; 1: 15-23. DOI: 10.21668/health.risk/2013.1.02.eng

Zaitseva N.V., Shur P.Z., May I.V., Kiryanov D.A. Approaches to the assessment of integrated health risk population based on evolution of mathematical models. Zdorov’e naseleniya i sreda obitaniya. 2011; 10: 6-9 (in Russian).

Onishchenko G.G., Zaitseva N.V., Zemlyanova M.A. Identification of health effects caused by environmental chemical exposure [Gigienicheskaya indikatsiya posledstvii dlya zdorov’ya pri vneshnesredovoi ekspozitsii khimicheskikh elementov]. Perm: Knizhnyy format; 2011: 532. (in Russian).

Zaitseva N.V., Ustinova O.Yu., Valina S.L. et al. Morbidity of the adult population in resident areas exposed to of aluminum and pulp-and-paper industry enterprises and associated with the chemical risk factors. Vestnik permskogo universiteta. Seriya: biologiya. 2017; 2: 222-9 (in Russian).

Brauer F., Castillo-Chavez C. Mathematical Models in Population Biology and Epidemiology (2nd ed.). Heidelberg: Springer Verlag; 2012: 522.

Lee H.Y., Topham D.J., Park S.Y., Hollenbaugh J., Treanor J., Mosmann T.R. et al. Simulation and prediction of the adaptive immune response to influenza A virus infection. J. Virol. 2009; 83(14): 7151-65.

Lehmann I., Sack U., Lehmann J. Metal ions affecting the immune system. Met. Ions Life Sci. 2011; 8: 157-85.

Bakirov A.B., Masyagutova L.M., Ribakov I.D., Immis S.M. Immunogenic body status as a criteria of adaptation for technological habital pollution (on the example of polimer chatalisators protuction). Meditsinskiy vestnik bashkortostana. 2008; 5: 23-9. (in Russian).

Kalinina O.L., Lakhman O.L., Zobnin Yu.V. Evaluation of the working conditions of the main occupations of the modern aluminic production. Sibirskiy meditsinskiy zhurnal. 2012; 6: 122-6. (in Russian).

Roslyi O.F., Fedoruk A.A., Slyshkina T.V. The issues of occupational health in modern aluminum electrolysis [Voprosy professional’nogo riska zdorov’yu v sovremennom elektrolize alyuminiya]. Mat. nauchno-prakticheskoi konferentsii. Novosibirsk: 2010; 2: 105-9. (in Russian).

Savilov E.D., Anganova E.V., Ilina S.V., Stepanenko L.A. echnogenic environmental pollution and the public health: analysis and prognosis. Gigiena i sanitariya. 2016; 6: 507-11. (in Russian).

Danilov I.P., Zakharenkov V.V., Oleshchenko A.M. et al. Occupational diseases in aluminium workers - possible ways of solving the problem. Acta Biomedica Scientifica. 2010; 4: 17-20. (in Russian).

Dolgikh O.V., Krivtsov A.V., Lykhina T.S., Bubnova O.A., Lanin D.V., Vdovina N.A., Luzhetsky K.P., Andreeva E.E. Features of the immune genetic parameters in workers in non-ferrous metal industry. Gigiena i sanitariya. 2015; 94(2): 54-7. (in Russian).

Shugaley I.V., Garabadzhiu A.V., Ilyushin M.A., Sudarikov A.M. Some aspects of effect of aluminium and its compounds on living organisms. Ekologicheskaya khimiya. 2012; 21(3): 168-72. (in Russian).

Zhu Y., Li Y., Miao L., Wang Y., Liu Y., Yan X., Cui X. et al. Immunotoxicity of aluminum. Chemosphere. 2014; 104: 1-6.

She Y., Wang N., Chen C., Zhu Y., Xia S., Hu C. et al. Effects of aluminum on immune functions of cultured splenic T and B lymphocytes in rats. Biol. Trace Elem. Res. 2012; 147: 246-50.

Zhu Y.Z., Liu D.W., Liu Z.Y., Li Y.F. Impact of aluminum exposure on the immune system: a mini review. Environ Toxicol Pharmacol. 2013; 35(1): 82-7.

Simbirtsev A.S. Cytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskiy akademicheskiy zhurnal. 2013; 3: 18-41. (in Russian).

Zaitseva G. A., Vershinia O.A., Matrokhina O. I., Senkina E. A., Karpova M.V. Cytokine status of the donors of blood and its components. Fundamental Research. 2011; 3: 61-5 (in Russian).

Bellinger D. L., Lorton D. Autonomic regulation of cellular immune function. Autonomic Neuroscience. 2014; 182: 15-41.

Calderón-Garcidueñas L., Cross J.V., Franco-Lira M. et al. Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrP (C)), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution. Front Neurosci. 2013; 10(7): 183-4.

Ignatov V. V. Сarbohydrate-recognizing proteins (lectins). Sorosovskij obrazovatel’nyj zhurnal. 1997; 2: 14-5. (in Russian).