Evaluation of the radioprotective properties of recombinant flagellin when used alone or in combination with interleukin-1 beta


Research objective. To evaluate the radioprotective effectiveness of recombinant flagellin when used alone or in combination with interleukin-1 beta for prophylactic or therapeutic effect on animals. Materials and methods. The effect of hybrid flagellin FliC Salmonella typhimurium and human interleukin-1β (Institute of Highly Pure Biopreparations, Saint Petersburg, Russia) on the 30-day survival of male mice exposed to lethal doses of X-ray radiation was studied. Survival of irradiated animals was analyzed by Kaplan-Meier method. Results. The preventive use of flagellin had a protective effect on the 30-day survival of mice irradiated with lethal doses of X-rays. Compared with the irradiated control, the administration of flagellin (1 mg/kg or 2 mg/kg) prior to X-ray exposure (7.5 Gy, 8.0 Gy or 8.5 Gy) increased the animal survival rate to 67-87%. Complex preventive administration of flagellin (1 mg/kg) and interleukin-1 beta (50 μg/kg) provided a 100% survival rate of the irradiated mice. Separate use of drugs was also effective; 92.8% of mice survived when flagellin was administered prior to irradiation and interleukin after. Conclusion. Recombinant flagellin is a promising candidate product for designing new generation of domestic radiation countermeasures, including combinations with interleukin-1 beta.

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About the authors

E V Murzina

S.M. Kirov Military Medical Academy

G A Sofronov

S.M. Kirov Military Medical Academy; Institute of Experimental Medicine

A S Simbirtsev

Institute of Experimental Medicine; Institute of Experimental Medicine; Research Institute of Highly Pure Biopreparations

N V Aksenova

S.M. Kirov Military Medical Academy

O M Veselova

S.M. Kirov Military Medical Academy

A M Ischenko

Research Institute of Highly Pure Biopreparations


  1. Рождественский Л.М. Актуальные вопросы поиска и исследования противолучевых средств // Радиационная биология. Радиоэкология. - 2013. - Т. 53. - № 5. - С. 513-520. [Rozhdestvenskiy LM. Aktual’nye voprosy poiska i issledovaniya protivoluchevykh sredstv. Radiats Biol Radioecol. 2013;53(5):513-520. (In Russ.)]
  2. Singh VK, Romaine PL, Seed TM. Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile. Health Phys. 2015;108(6):607-630. doi: 10.1097/HP.0000000000000279.
  3. Kamran MZ, Ranjan A, Kaur N, et al. Radioprotective Agents: Strategies and Translational Advances. Med Res Rev. 2016;36(3):461-493. doi: 10.1002/med.21386.
  4. Гребенюк А.Н., Аксенова Н.В., Петров А.В., и др. Получение различных вариантов рекомбинантного флагеллина и оценка их радиозащитной эффективности // Вестник Российской военно-медицинской академии. - 2013. - Т. 43. - № 3. - С. 75-80. [Grebenyuk AN, Aksenova NV, Petrov AV, et al. Expression of different variants of recombinant flagellin and study of their radioprotective efficacy. Vestnik Rossiiskoi voenno-meditsinskoi akademii. 2013;43(3):75-80. (In Russ.)]
  5. Гребенюк А.Н., Легеза В.И. Противолучевые свойства интерлейкина-1. - СПб.: Фолиант, 2012. [Grebenyuk AN, Legeza VI. Protivoluchevye svoystva interleykina-1. Saint Petersburg: Foliant; 2012. (In Russ.)]
  6. Боровиков В.П. Популярное введение в современный анализ данных в системе Statistica. - M.: Горячая линия-Телеком, 2013. [Borovikov VP. Populyarnoe vvedenie v sovremennyy analiz dannykh v sisteme STATISTICA. Moscow: Goryachaya liniya-Telekom; 2013. (In Russ.)]
  7. Мурзина Е.В., Софронов Г.А., Аксенова Н.В., и др. Экспериментальная оценка противолучевой эффективности рекомбинантного флагеллина // Вестник Российской военно-медицинской академии. - 2017. - Т. 59. - № 3. - С. 122-128. [Murzina EV, Sofronov GA, Aksenova NV, et al. Experimental estimation of the radioprotective efficiency of recombinant flagellin. Vestnik Rossiiskoi voenno-meditsinskoi akademii. 2017;59(3):122-128. (In Russ.)]
  8. Симбирцев А.С. Интерлейкин-1. Физиология, патология, клиника. - СПб.: Фолиант, 2011. [Simbirtsev AS. Interleykin-1. Fiziologiya, patologiya, klinika. Saint Petersburg: Foliant; 2011. (In Russ.)]
  9. Vijay-Kumar M, Aitken JD, Sanders CJ, et al. Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. J Immunol. 2008;180(12):8280-8285. doi: 10.4049/jimmunol.180.12.8280.
  10. Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008;320(5873):226-230. doi: 10.1126/science.1154986.
  11. Krivokrysenko VI, Toshkov IA, Gleiberman AS, et al. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates. PLoS One. 2015;10(9):e0135388. doi: 10.1371/journal.pone.0135388.
  12. Singh VK, Garcia M, Seed TM. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status. Int J Radiat Biol. 2017;93(9):870-884. doi: 10.1080/09553002.2017.1338782.
  13. Krivokrysenko VI, Shakhov AN, Singh VK, et al. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther. 2012;343(2):497-508. doi: 10.1124/jpet.112.196071.
  14. Lopez-Yglesias AH, Zhao X, Quarles EK, et al. Flagellin induces antibody responses through a TLR5- and inflammasome-independent pathway. J Immunol. 2014;192(4):1587-1596. doi: 10.4049/jimmunol.1301893.
  15. Hoffmann A, Baltimore D. Circuitry of nuclear factor kappa B signaling. Immunol Rev. 2006;210:171-186. doi: 10.1111/j.0105-2896.2006.00375.x.
  16. Chen H, Wang ZD, Chen MS, et al. Activation of Toll-like receptors by intestinal microflora reduces radiation-induced DNA damage in mice. Mutat Res Genet Toxicol Environ Mutagen. 2014;774:22-28. doi: 10.1016/j.mrgentox.2014.09.001.
  17. Li W, Ge C, Yang L, et al. CBLB502, an agonist of Toll-like receptor 5, has antioxidant and scavenging free radicals activities in vitro. Int J Biol Macromol. 2016;82:97-103. doi: 10.1016/j.ijbiomac.2015.10.033.
  18. Wang Z-D, Qiao Y-L, Tian X-F, et al. Toll-like Receptor 5 Agonism Protects Mice from Radiation Pneumonitis and Pulmonary Fibrosis. Asian Pac J Cancer Prev. 2012;13(9):4763-4767. doi: 10.7314/apjcp.2012.13.9.4763.
  19. Zhou S-X, Li F-S, Qiao Y-L, et al. Toll-like Receptor 5 Agonist Inhibition of Growth of A549 Lung Cancer Cells in Vivo in a Myd88 Dependent Manner. Asian Pac J Cancer Prev. 2012;13(6):2807-2812. doi: 10.7314/apjcp.2012.13.6.2807.
  20. Toshkov IA, Gleiberman AS, Mett VL, et al. Mitigation of Radiation-Induced Epithelial Damage by the TLR5 Agonist Entolimod in a Mouse Model of Fractionated Head and Neck Irradiation. Radiat Res. 2017;187(5):570-580. doi: 10.1667/RR14514.1.
  21. Liu Z, Lei X, Li X, et al. Toll-like receptors and radiation protection. Eur Rev Med Pharmacol Sci. 2018;22(1):31-39. doi: 10.26355/eurrev_201801_14097.
  22. Brackett CM, Kojouharov B, Veith J, et al. Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis. Proc Natl Acad Sci U S A. 2016;113(7):E874-883. doi: 10.1073/pnas.1521359113.
  23. Kojouharov BM, Brackett CM, Veith JM, et al. Toll-like receptor-5 agonist Entolimod broadens the therapeutic window of 5-fluorouracil by reducing its toxicity to normal tissues in mice. Oncotarget. 2014;5(3):802-814. doi: 10.18632/oncotarget.1773.



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