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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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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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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DOI: https://doi.org/10.1134/S1062359022110103