Immunotropic effects of nitrogenous metabolites (creatinine, urea, uric acid and bilirubin) in humans exposed to the factors of the accident at the Chоrnobyl nuclear power plant

Igor Kuchma, Anatoliy Gozhenko, Volodymyra Bilas, Sofiya Ruzhylo, Galyna Kovalchuk, Yaryna Nahurna, Walery Zukow, Igor Popovych



Background. In previous studies, we found that nitrogenous metabolites exhibit significant immunotropic activity, both suppressor and enhancing, at healthy rats. The purpose of this and our subsequent research is to elucidate the links between nitrogenous metabolites and immune parameters in different categories of people, both healthy and sick. Material and methods. The object of observation in 1997 were 19 men and 3 women who were exposed to pathogenic factors of the accident at the Chоrnobyl nuclear power plant during the liquidation of its consequences in 1986-87. The survey was conducted twice - on admission and after two weeks of rehabilitation at the Truskavets’ Spa. The plasma and urinary concentration of the nitrogenous metabolites were determined. Immune status was assessed on tests of I and II levels according to the WHO memorandum. Results. Both negative and positive metabolic-immune correlations were revealed. Calculation of multiple correlation coefficients between individual metabolite parameters and constellations of immune parameters revealed the maximum immunotropic effect of Urea urine (R=0,756). This is followed by Uric acid plasma (R=0,727) and urine (R=0,691), Urea plasma (R=0,622), Creatinine plasma (R=0,588), Bilirubinemia (R=0,546) and Creatinine urine (R=0,510). The canonical correlation between the constellation of nitrogenous metabolites, on the one hand, and the parameters of immunity, on the other hand, was very strong: R=0,971; χ2(15)=239; p<10-5. Conclusion. Nitrogenous metabolites have immunomodulatory effects, both suppressor and enhancing, both in healthy rats and in humans exposed to pathogenic influences.


urea; uric acid; creatinine; bilirubin; immunity; relationships; humans.

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Apasov S, Chen JF, Smith P, Sitkovsky M. A2A receptor dependent and A2A receptor independent effects of extracellular adenosine on murine thymocytes in condicion of adenosine deaminase deficiency. Blood. 2000; 95(12): 3859-3867.

Avilla MN, Malecki KMC, Hahn ME, Wilson RH, Bradfield CA. The Ah Receptor: Adaptive Metabolism, Ligand Diversity, and the Xenokine Model. Chem Res Toxicol. 2020; 33(4): 860-879.

Bianco C. Population of lymphocytes bearing a membrane receptor for antigen-antibody complex. J Exp Med. 1970; 134(4): 702-720.

Bilas VR, Popovych IL. Role of microflora and organic substances of water Naftussya in its modulating influence on neuroendocrine-immune complex and metabolism [in Ukrainian]. Medical Hydrology and Rehabilitation. 2009; 7(1): 68-102.

Carvalho LAC, Lopes JPPB, Kaihami GH, Silva RP, Bruni-Cordoso A, Baldini RL, Meotti FC. Uric acid disrupts hypochlorous acid production and bactericidal activity of HL-60 cells. Redox Biology. 2018; 16: 179-188.

Climaco-Arvizu S, Domínguez-Acosta O, Cabañas-Cortés MA, et al. Aryl hydrocarbon receptor influences nitric oxide and arginine production and alters M1/M2 macrophage polarization. Life Sci. 2016; 155: 76-84.

Díaz-Díaz CJ, Ronnekleiv-Kelly SM, Nukaya M, et al. The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse. Ann Surg. 2016; 264(3): 429-436.

Douglas SD, Quie PG. Investigation of Phagocytes in Disease. Churchil; 1981: 110 p.

Esser C, Rannug A. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol Rev. 2015; 67(2): 259-279.

Gao L, Jiang Y, Wang Y, Qu X, Li L, Lou X, Wang Y, GuoW, Liu Y. Male asymptomatic hyperuricemia patients display a lower number of NKG2D+ NK cells before and after a low-purine diet. Medicine (Baltimore). 2018; 97(50): e13668.

Ghaemi-Oskouie F, Shi Yan. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep. 2011; 13(2): 160-166.

Goryachkovskiy АМ. Clinical Biochemistry [in Russian]. Odesa: Astroprint; 1998: 608 p.

Gozhenko AI. Functional-metabolic continuum [in Russian]. J of NAMS of Ukraine. 2016; 22 (1): 3-8.

Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Functional relationships between parameters of uric acid exchange and immunity in female rats. Actual problems of transport medicine. 2019; 4(58): 123–131.

Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Features of immune status in different states of uric acid metabolism in female rats. Journal of Education, Health and Sport. 2019; 9(12): 167-180.

Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. Relationships between parameters of uric acid exchange and immunity as well as microbiota in patients with neuroendocrine-immune complex dysfunction. Journal of Education, Health and Sport. 2020; 10(1): 165-175.

Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. Relationships between changes in uric acid parameters metabolism and parameters of immunity and microbiota in patients with neuroendocrine-immune complex dysfunction. Journal of Education, Health and Sport. 2020; 10(2): 212-222.

Gozhenko AI, Zukow W, Polovynko IS, Zajats LM, Yanchij RI, Portnichenko VI, Popovych IL. Individual Immune Responses to Chronic Stress and their Neuro-Endocrine Accompaniment. RSW. UMK. Radom. Torun; 2019: 200 p.

Hoskin DW, Mader JS, Furlong SJ, Conrad DM, Blay J. Inhibition of T cell and NK cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol. 2008; 32(3): 527-535.

Huang S, Apasov S, Koshiba M, SitkovskiM. Role of A2A extracellular adenosine receptor mediated signaling in adenosine mediated inhibition of of T-cell activation and expansion. Blood. 1997; 90(4): 1600-1610.

Jondal M, Holm G, Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972; 136(2): 207-215.

Kostyuk PG, Popovych IL, Іvassivka SV (editors). Chornobyl’, Adaptive and Defensive Systems, Rehabilitation [in Ukrainian]. Kyiv. Computerpress; 2006: 348 p.

Limatibul S, Shore A, Dosch HM, Gelfand EW. Theophylline modulation of E-rosette formation: an indicator of T-cell maturation. Clin Exp Immunol. 1978; 33(3): 503-513.

Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965; 2(3): 235-254.

Martínez-Reyes CP, Manjarrez-Reyna AN, Méndez-García LA, et al. Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1. Biomolecules. 2020; 10(4): 576.

Morelli M, Carta AR, Kachroo A, Schwarzschild A. Pathophysiological roles for purines: adenosine, caffeine and urate. Prog Brain Res. 2010; 183: 183-208.

Navalta JW, Fedor EA, Schafer MA, Lyons TS, Tibana RA, Pereira GB, Prestes J. Caffeine affects CD8+ lymphocyte differently in naїve and familiar individuals following moderate intensity exercise. Int J Immunopathol Pharmacol. 2016; 29(2): 288-294.

Perederiy VG, Zemskov AM, Bychkova NG, Zemskov VM. Immune status, principles of its evaluation and correction of immune disorders [in Russian]. Kyiv. Zdorovya; 1995: 211 p.

Phelan D, Winter GM, Rogers WJ, Lam JC, Denison MS. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch Biochem Biophys. 1998; 357(1): 155-163.

Popadynets’ OO, Gozhenko AI, Zukow W, Popovych IL. Relationships between the entropies of EEG, HRV, immunocytogram and leukocytogram. Journal of Education, Health and Sport. 2019; 9(5): 651-666.

Popovych IL, Flyunt IS, Alyeksyeyev OI, Barylyak LG, Bilas VR. Sanogenetic Bases of Rehabilitation on Spa Truskavets’ Urological Patients from Chornobylian Contingent [in Ukrainian]. Kyiv. Computerpress; 2003: 192 p.

Popovych IL, Gozhenko AI, Kuchma IL, Zukow W, Bilas VR, Kovalchuk GY, Ivasivka AS. Immunotropic effects of so-called slag metabolites (creatinine, urea, uric acid and bilirubin) at rats. Journal of Education, Health and Sport. 2020; 10(11): 320-336.

Quintana FJ, Sherr DH. Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev. 2013; 65(4): 1148-1161.

Romodanov AP (editor). Postradiation Encephalopathy. Experimental Researches and Clinical Observations [in Ukrainian and Russian]. Kyiv. USRI of Neurosurgery; 1993: 224 p.

Smagliy VS, Gozhenko AI, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. Variants of uric acid metabolism and their immune and microbiota accompaniments in patients with neuroendocrine-immune complex dysfunction. Actual problems of transport medicine. 2020; 1(59): 114–125.

Vigano S, Alatzoglou D, Irving M, Menetrier-Caux Ch, Caux Ch, Romero P, Coukos G. Targeting adenosine in cancer immunotherapy to enhance T-cell function. Front Immunol. 2019; 10: 925.

Yang X, Liu H, Ye T, et al. AhR activation attenuates calcium oxalate nephrocalcinosis by diminishing M1 macrophage polarization and promoting M2 macrophage polarization. Theranostics. 2020; 10(26): 12011-12025.

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1223 Journal of Education, Health and Sport eISSN 2391-8306 7

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