Cytokine profile of patients with severe hemorrhagic fever complicated with acute renal failure

Objective: to determine the cytokine profile in blood serum in patients with severe hemorrhagic fever complicated by acute renal failure. 

Materials and methods. The examined persons were divided into a control group – 46 people (healthy), a group of patients with an average course of the disease – 35 people, and a group of patients with severe severity, complicated by acute renal failure – 38 people. Blood was taken from the subjects for the study of cytokines. The determination of cytokines was carried out by enzyme immunoassay using test kits in accordance with the manufacturer’s instructions.  

Results. In patients with hemorrhagic fever, both with moderate and severe, there was an increase in interleukins IL-1β, IL-6, IL-10 compared with the control group. However, the values of these interleukins were significantly higher in patients with severe hemorrhagic fever complicated by acute renal failure compared with the group of patients with moderate severity. The values of IL-8, IFN-γ and SDF-1α changed only in patients with severe course. At the same time, there was an increase in the expression of IL-8 and a decrease in IFN-γ compared with the control group. IL-8 and IFN-γ did not change statistically in patients who had just been admitted to the hospital, as well as in patients with an average degree of the disease. A change in the SDF-1α chemokine also turned out to be specific for patients with a severe course of the disease: its values increased in comparison with the control group. No significant changes in SDF-1α were detected in patients who had just been admitted to the hospital, as well as in the group of patients with moderate severity of the disease.  

Conclusion. The results obtained indicate the diagnostic value of cytokine determination in severe hemorrhagic fever complicated by acute renal failure. Changes in the parameters of some cytokines, detected only in the profile of patients with severe severity, require further research to clarify their role in the pathogenesis of hemorrhagic fever, and also open up opportunities for considering them as biomarkers. 

1. Liem T, Cressler D. Bui-Mansfield Imaging of Hemorrhagic Fever With Renal Syndrome: A Potential Bioterrorism Agent of Military Significance. Military Medicine. 2011; 176 (11):1327-1334. DOI:10.7205/MILMED-D-11-00048.

2. Jiang H, et al. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture. Front Cell Infect Microbiol. 2016; 3 (6):1. DOI: 10.3389/fcimb.2016.00001.

3. Kellum JA, et al. Acute kidney injury. Nat Rev Dis Primers. 2021; Vol.7. DOI: 10.1038/s41572-021-00284-z

4. Meijers B, Evenepoel P, Anders HJ. Intestinal microbiome and fitness in kidney disease. Nature Reviews Nephrology. 2019; 15:531–545.

5. Lee SA, Cozzi M, Bush EL, Rabb H. Distant organ dysfunction in acute kidney injury: a review. American Journal of Kidney Diseases. 2018; 72: 846–856. DOI: 10.1053/j. ajkd.2018.03.028

6. Gilyazova IR, et al. Association of polymorphic variant RS1127327 of the target gene microRNA-146a ccdc6 with a reduced risk of developing severe hemorrhagic fever with renal syndrome in patients from the Volga-Ural region of Russia. Yakutskij medicinskij zhurnal. 2022; 2 (78):5-8. (In Russ.) http:// ymj.mednauka.com/files/YMJ-2022-2.pdf

7. Anisimova TA, Karzakova LM. Dynamics of immunological and laboratory parameters in patients with hemorrhagic fever with renal syndrome in various forms of severity // Sovremennye problemy nauki i obrazovani ya. 2012; 4. (In Russ.) https://science-education.ru/ru/ article/view?id=6857

8. Grigoriev DN, et al. Local and systemic inflammatory transcriptome after acute kidney injury. J Am Soc Nephrol. 2008; 19:547-558. DOI: 10.1681/ASN.2007040469.

9. Ma H, et al. The long noncoding RNA NEAT1 exerts antihantaviral effects by acting as positive feedback for RIG-I signaling. Journal of Virology. 2017; 91 (9). DOI: https://doi. org/10.1128/JVI.02250-16.

10. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008; 28 (4): 454-467. DOI: 10.1016/j.immuni.2008.03.004.

11. Tominaga K, et al. IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol. 2000; 12 (2):151-160. DOI: 10.1093/intimm/12.2.151.

12. Schooling CM, Li M, Au Yeung SL. Interleukin-18 and COVID-19. Epidemiol Infect. 2021; 150:e14. DOI: 10.1017/ S0950268821002636.

13. Galimova EF, et al. Imbalance of chemokines and growth factors in the pathogenesis of male infertility. Rossijskij Immunologicheskij ZHurnal. 2017; 11 (20): 273-275. (In Russ.) https://rusimmun.ru/jour/article/view/652/540

14. Su H, Lei CT, Zhang C, Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol. 2017; 8:405. DOI: 10.3389/fimmu.2017.00405.

15. Chen QZ, et al. HTNV-induced upregulation of miR146a in HUVECs promotes viral infection by modulating proinflammatory cytokine release. W. Biochem Biophys Res Commun. 2017; 493 (1): 807-813.

16. Raftery MJ, et al. Replication in the Mononuclear Phagocyte System (MPS) as a Determinant of Hantavirus Pathogenicity. Front Cell Infect Microbiol. 2020; 10: 281. DOI: 10.3389/ fcimb.2020.00281.

17. Galimov ShN, Galimova EF, Pavlov VN. Cytokine spectrum of blood serum and sperm plasma in idiopathic infertility. Permskij medicinskij zhurnal. 2012; 29(6): 58-63. (In Russ.)

18. Karzakova LM, et al. Features of the production of cytokines in different periods of hemorrhagic fever with renal syndrome. Acta Medica Eurasica. – 2016; 3: 22-28. (In Russ.)

19. Martynenko AYu, Tomilka GS, Obukhova GG. Dynamics of cytokines in hemorrhagic fever with renal syndrome. Dal’nevostochnyj medicinskij zhurnal. 2015; 4: 47-50. (In Russ.)

20. Uskova YuG, Pavelkina VF. Dynamics of immunological parameters in patients with hemorrhagic fever with renal syndrome of varying severity. Prakticheskaya medicina.2016; 3 (95):99-103. https://elibrary.ru/download/elibrary_26153225_39628426.pdf

21. Cui L, et al. Stromal-derived factor-1 and its CXCR4 receptor in adult neurogenesis after cerebral ischemia. Restor Neurol Neurosci. 2013; 31: 239-251. (In Russ.) DOI: 10.3233/RNN-120271

22. Cheng Xi, et al. The role of SDF-1/CXCR4/CXCR7 in the regeneration of neurons after cerebral ischemia Front Neurosci. 2017;11:590. DOI: 10.3389/fnins.2017.00590

23. Yuang X, et al. The stromal cell-derived factor-1 α (SDF1α)/cysteine-X-cysteine chemokine receptor 4 (CXCR4) axis: a possible prognostic indicator of acute ischemic stroke. J Int Med. 2019; 7 (5): 1897-1907. DOI: 10.1177/0300060519827173.