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The Cytokine Profile of Chronically Irradiated People in the Long Term after the Beginning of Irradiation

  • RADIATION IMMUNOLOGY
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Abstract

The cytokine network is an important integrative and regulatory mechanism of the immune, endocrine, and nervous systems. Disturbances of this mechanism could play a role in the development of long-term biological effects of ionizing radiation at the subcellular, cellular, and whole body levels. Changes in the immune system of chronically exposed people, including specific features of the cytokine profile, were noted decades after the onset of exposure and were more pronounced in prenatally exposed individuals. The aim of this study was to assess the concentrations of certain cytokines in the blood serum of chronically exposed residents of the riverside villages of the Techa River 65–68 years after the onset of radiation exposure and correlations of the revealed changes with the dose to red bone marrow (RBM) and certain nonradiation factors. 406 people from the Techa River cohort (main group) were examined. Mean cumulative dose estimated for RBM in this group was 950.4 mGy; the median age of the patients was 70.0 years. Mean cumulative dose to RBM for 149 unexposed people included in the comparison group was 23.5 mGy; the median age of patients in this group was 68.5 years. The groups did not have statistically significant differences in age, sex, ethnic composition, or socio-economic living conditions of the people. The concentrations of IL-1β, IL-1(RA), IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, IFNα, and IFNγ in the blood serum were assessed using enzyme-linked immunosorbent assay. Chronically exposed individuals were revealed to have a statistically significant increase in the content of three proinflammatory cytokines: IL-8 (3.12 pg/mL, p = 0.010), TNFα (4.40 pg/mL, p = 0.010), and IFNγ (10.67 pg/mL, p = 0.040) relative to unexposed people (2.28, 3.61 and 8.34 pg/mL, respectively) and a decrease in the concentration of the main anti-inflammatory cytokines. Thus, the content of IL-4 in the main group was 1.14 pg/mL versus 3.48 pg/mL in the comparison group (p = 0.010), and the level of IL-10 was 6.18 pg/mL relative to 7.52 pg/mL in unexposed people (p = 0.010). The serum concentrations of IL-1β, IL-1α, IL-1(RA), IL-2, IL-6, CSF-GM, CSF-G, and IFNα did not differ in either group. The content of TNFα in the blood serum was weakly positively correlated with the individual cumulative dose of RBM exposure (SR = 0.14, p = 0.003). The concentrations of IL-4, IL-10, and IFNγ showed a weak negative correlation with the age of the examined people of the main group (SR = ‒0.19, p < 0.001; SR = –0.12, p = 0.020 and SR = –0.16, p = 0.002, respectively). In the comparison group, IL-4 correlated with age weakly negatively (SR = –0.30, p < 0.001), and IFNγ correlated with it weakly positively (SR = 0.18, p = 0.040). The level of IL-8 in the comparison group correlated weakly negatively with sex (SR = –0.18, p = 0.030); in the main group such a relationship was not found. Chronically exposed people were revealed to have proinflammatory changes in the serum cytokine profile with signs of an imbalance 65–68 years after the start of exposure. These changes did not depend (for most parameters) or depended little of the dose of RBM exposure (TNFα concentration) and the age (IL-4, IL-10, and IFNγ concentrations) of patients.

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REFERENCES

  1. Stewart, F.A., Akleyev, A.V., Hauer-Jensen, M., et al., Early and Late Effects of Radiation in Normal Tissues and Organs—Threshold Doses for Tissue Reactions in a Radiation Protection Context, ICRP Publication 118, Ann. ICRP, 2012, 41(1/2), Amsterdam: Elsevier, 2012.

  2. Sennikova, J.A., Grishina, L.V., Gelfgat, E.L., et al., The distant consequence of low radiation doses influence on human immune system, Byull. VSNC SO RAMN, 2005, no. 2 (116), pp. 59–64.

  3. Schaue, D., Kachikwu, E.L., and McBride, W.H., Cytokines in radiobiological responses: a review, Radiat. Res., 2012, vol. 178, pp. 505–523. https://doi.org/10.1667/RR3031.1

    Article  PubMed  PubMed Central  Google Scholar 

  4. Posledstviya radioaktivnogo zagryazneniya reki Techi (Consequences of Radioactive Contamination of the Techa River), Aklеуеv, A.V., Ed., Chelyabinsk: Kniga, 2016.

    Google Scholar 

  5. Aklеуеv, A.A. and Dolgushin, I.I., Immune status of persons with CRS at later time points, Radiats. Risk, 2018, vol. 27, no. 2, pp. 76–85. https://doi.org/10.21870/0131-3878-2018-27-2-76-85

    Article  Google Scholar 

  6. Aklеуеv, A.A., Blinova, E.A., and Kotikova, A.I., Features of the cytokine profile and relationships of polymorphisms of the immune system with levels of serum cytokines in individuals exposed to chronic radiation exposure, Ross. Immunol. Zh., 2018, vol. 12, no. 3, pp. 199–204. https://doi.org/10.31857/S102872210002381-4

    Article  Google Scholar 

  7. Hayashi, T., Morishita, Y., Kubo, Y., et al., Long-term effects of radiation dose on inflammatory markers in atomic bomb survivors, Am. J. Med., 2005, vol. 118, no. 1, pp. 83–86. https://doi.org/10.1016/j.amjmed.2004.06.045

    Article  PubMed  Google Scholar 

  8. Senyuk, O.F., Kavsan, V.M., Muller, W.E., et al., Long-term effects of low-dose irradiation on human health, Cell. Mol. Biol., 2002, no. 4, pp. 393–409.

  9. Attar, M., Molaie, K.Y., and Khansari, N., Effect of high dose natural ionizing radiation on the immune system of the exposed residents of Ramsar Town, Iran, Iran. J. Allergy, Asthma Immunol., 2007, vol. 6, no. 2, pp. 73–78.

    CAS  PubMed  Google Scholar 

  10. Akleyev, A.V., Chronic Radiation Syndrome, Berlin-Heidelberg: Springer, 2014.

    Book  Google Scholar 

  11. Degteva, M.O., Napier, B.A., Tolstykh, E.I., et al., Distribution of individual doses in a cohort of people irradiated as a result of radioactive contamination of the Techa River, Med. Radiol. Radiats. Bezop., 2019, vol. 64, no. 3, pp. 46–53. https://doi.org/10.12737/article_5cf2364cb49523.98590475

    Article  Google Scholar 

  12. Gosudarstvennye sanitarno-epidemiologicheskie pravila i normativy. SanPiN 2.6.1.2523-09. Normy radiatsionnoi bezopasnosti (NRB-99/2009) (State Sanitary and Epidemiological Rules and Regulations. SanPiN 2.6.1.2523-09. Radiation Safety Standards (NRB-99/2009)), Moscow: Federal’nyi tsentr gigieny i epidemiologii Rospotrebnadzora, 2009.

  13. Kishkun, A.A., Gilmanov, A.Zh., Dolgikh, T.I., et al., Organization of the preanalytical stage in the centralization of laboratory research: guidelines, Poliklinika, 2013, no. 2, pp. 6–27.

  14. Glantz, S., Primer of Biostatistics, New York: McGraw-Hill, 2011.

    Google Scholar 

  15. Grzhibovsky, A.M., Ivanov, S.V., and Gorbatova, M.A., Ecological (correlation) studies in health care, Nauka Zdravookhr., 2015, no. 5, pp. 5–18.

  16. Grzhibovsky, A.M., Ivanov, S.V., and Gorbatova, M.A., Correlation analysis of data using Statistica and SPSS software, Nauka Zdravookhr., 2017, no. 1, pp. 7–36.

  17. Azimian, H., Bahreyni-Toossi, M.T., and Rezaei, A.R., Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation, J. Med. Phys., 2015, vol. 40, no. 1, pp. 38–44. https://doi.org/10.4103/0971-6203.152249

    Article  PubMed  PubMed Central  Google Scholar 

  18. Devic, C., Ferlazzo, M.L., and Foray, N., Influence of individual radiosensitivity on the adaptive response phenomenon: toward a mechanistic explanation based on the nucleo-shuttling of ATM protein, Dose Response, 2018, vol. 16, no. 3, p. 1559325818789836. https://pubmed.ncbi.nlm.nih.gov/30093841/. Accessed October 25, 2020.https://doi.org/10.1177/1559325818789836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Osnovy radiobiologii i radiatsionnoi meditsiny (Fundamentals of Radiobiology and Radiation Medicine), Grebenyuk, A.N., Strelova, O.Yu., Legeza, V.I., et al., Eds., St. Petersburg: Foliant, 2012.

    Google Scholar 

  20. Bogdándi, E.N., Balogh, A., Felgyinszki, N., et al., Effects of low-dose radiation on the immune system of mice after total-body irradiation, Radiat. Res., 2010, vol. 174, no. 4, pp. 480–489. https://doi.org/10.1667/RR2160.1

    Article  CAS  PubMed  Google Scholar 

  21. Samotrueva, M.A., Yasenyavskaya, A.L., Tsibizova, A.A., et al., Neuroimmunoendocrinology: modern concepts of molecular mechanisms, Immunologiya, 2017, vol. 38, no. 1, pp. 49–59. https://doi.org/10.18821/0206-4952-2017-38-1-49-59

    Article  Google Scholar 

  22. Kusunoki, Y., Yamaoka, M., Kubo, Y., et al., T-cell immunosenescence and inflammatory response in atomic bomb survivors, Radiat. Res., 2010, vol. 174, no. 6, pp. 870–876. https://doi.org/10.1667/RR1847.1

    Article  CAS  PubMed  Google Scholar 

  23. Nakachi, K., Hayashi, T., Imai, K., et al., Perspectives on cancer immune-epidemiology, Cancer Sci., 2004, vol. 95, no. 12, pp. 921–929. https://doi.org/10.1111/j.1349-7006.2004.tb03178.x

    Article  CAS  PubMed  Google Scholar 

  24. Park, H.R. and Jo, S.K., Lasting effects of an impairment of th1-like immune response in gamma-irradiated mice: a resemblance between irradiated mice and aged mice, Cell. Immunol., 2011, vol. 267, no. 1, pp. 1–8. https://doi.org/10.1016/j.cellimm.2010.10.004

    Article  CAS  PubMed  Google Scholar 

  25. Feng, L., Qin, L., Guo, D., et al., Immunological mechanisms of low-dose priming radiation resistance in walker-256 tumor model mice, Exp. Ther. Med., 2017, vol. 14, no. 4, pp. 3868–3873. https://doi.org/10.3892/etm.2017.4975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Greenberger, J.S., Epperly, M.W., Zeevi, A., et al., Stromal cell involvement in leukemogenesis and carcinogenesis, In Vivo, 1996, vol. 10, no. 1, pp. 1–17.

    CAS  PubMed  Google Scholar 

  27. Coates, P.J., Rundle, J.K., Lorimore, S.A., et al., Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling, Cancer Res., 2008, vol. 68, no. 2, pp. 450–456. https://doi.org/10.1158/0008-5472.CAN-07-3050

    Article  CAS  PubMed  Google Scholar 

  28. Lorimore, S.A., Chrystal, J.A., Robinson, J.I., et al., Chromosomal instability in unirradiated hematopoietic cells induced by macrophages exposed in vivo to ionizing radiation, Cancer Res., 2008, vol. 68, no. 19, pp. 8122–8126. https://doi.org/10.1158/0008-5472.CAN-08-0698

    Article  CAS  PubMed  Google Scholar 

  29. Lorimore, S.A., Mukherjee, D., Robinson, J.I., et al., Long-lived inflammatory signaling in irradiated bone marrow is genome dependent, Cancer Res., 2011, vol. 71, no. 20, pp. 6485–6491. https://doi.org/10.1158/0008-5472.CAN-11-1926

    Article  CAS  PubMed  Google Scholar 

  30. Hanahan, D. and Weinberg, R.A., Hallmarks of cancer: the next generation, Cell, 2011, vol. 144, no. 5, pp. 646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

The authors would like to thank the staff of the URCRM for help in forming the study groups and technical assistance during the study: head of the department the Database “Man” N.V. Startsev and senior laboratory assistant of the laboratory of Molecular and Cellular Radiobiology N.P. Litvinenko.

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Correspondence to E. A. Kodintseva.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Kodintseva, E.A., Akleyev, A.A. & Blinova, E.A. The Cytokine Profile of Chronically Irradiated People in the Long Term after the Beginning of Irradiation. Biol Bull Russ Acad Sci 49, 2143–2149 (2022). https://doi.org/10.1134/S1062359022110103

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