Level of IL-1β, TNF-α, IL-4 and IL-10 in TLR2(ARG753GLN), TLR4(ASP299GLY) SNP carriers with brain injury

Оbjective: to study the effect of polymorphism of the TLR2-753(Arg>Gln), TLR4-299(Asp>Gly) genes for the content of IL-1β, TNF-α, IL-4 and IL-10 in patients with a cerebral contusion.

Materials and methods. 96 young patients (according to WHO classification) with cerebral contusion were examined. The first group (n=50) was compiled by patients with a contusion of moderate severity at the age of 29.5 [24; 33] years. The second (n=46) - patients with a severe degree (average age 32.5 [28.5; 35] years), and in this group in 10 patients an unfavorable outcome (exitus. letalis) was registered. The control group is 100 practically healthy residents of the same sex and age. Patients with any acute and/or chronic concomitant pathology, as well as females, were excluded from the study. Clinical, laboratory (genes polymorphism: TLR2-753(Arg>Gln), TLR4-299(Asp>Gly); Citokine content: IL-1β, TNF-α, IL-4, IL-10) and instrumental (craniography, computed tomography) the studies were carried out at the inpatient stage of treatment (the fence of the material for the study was performed for 3 days after the injury). Statistical processing of research results was carried out using the IBM SPSS Statistics Version 25.0 program.

Results. Allele -753Arg- and genotype -753Arg/Arg prevailed in the control group (82.5% and 65%, respectively) and in patients with moderate cerebral contusion (100%), while in the group of patients with severe cerebral contusion, the allele - 753Gln- (60.9%) and heterozygous -753ArgGln genotype (78.3%). The mutant genotype -753Gln/Gln of the gene under consideration was detected only in the group of patients with severe cerebral contusion and in the group with a fatal outcome (21.7% and 100%, respectively). The presence of -299Asp- allele in the control group was detected in 67.5% of residents, in patients with favorable outcome of cerebral contusion in 66.3% of cases and in 100% of patients with unfavorable outcome. In all patients with a fatal TBI, 100% had a homozygous -299AspAsp genotype. It was shown that in patients with cerebral contusion on the 3rd day after injury, the content of such parameters as IL-1β, TNF-α, IL-4 and IL-10 significantly exceeded the control values by 1.3, 1.3, 1.2 and 1, 1 times, respectively, while in patients with an unfavorable course of cerebral contusion in dynamics (St. letalis), in comparison with the group of cerebral contusion with a favorable course (recovery), their level significantly exceeded the control values by 2, 2, 1.6 and 1.3 times , respectively.

Conclusion. The presence of the -299Asp/Asp genotype of the TLR4-299Asp>Gly gene polymorphism indirectly contributes to a higher serum level of the cytokine IL-1β, TNF-α, IL-4 and IL-10. When carrying the -753Gln/Gln mutant genotype of the TLR2-753Arg>Gln gene polymorphism, one can state a significant effect of their carriage on a higher content of the studied cytokines in the blood serum.

1. Pellot J.E., Jesus O.D. Cerebral contusion. Treasure Island (FL): StatPearls Publishing. 2021. https://www.ncbi.nlm.nih.gov/books/NBK562147/. PMID 32965818. Bookshelf ID: NBK562147.

2. Krohaleva Yu.A., Stambovskaya N.N. Carriage of genetic polymorphisms in TLR2, TLR3 and the concentration of IL-1Β, IL-6 in plasma of patients with cerebral stroke Far East Medical Journal. 2016. 1. 59-62. URL: http://eport.fesmu.ru/dmj/20161/2016114.aspx (date of the application: 04.07.2022). in Russian.

3. Krohaleva Yu.A., Stambovskaya N.N. The prevalence of genetic polymorphisms of toll-like receptors and the concentration of IL-1β, IL-6 in plasma of patients with cerebral stroke. Advances in current natural sciences. 2015. 7. 7–11. URL: https://natural-sciences.ru/ru/article/view?id=35479 (дата обращения: 04.07.2022). in Russian.

4. Adatia K., Newcombe V.F.J., Menon D.K. Contusion Progression Following Traumatic Brain Injury: A Review of Clinical and Radiological Predictors, and Influence on Outcome. Neurocrit Care. 2021. 34(1). 312-324. doi: 10.1007/s12028-020-00994-4.

5. Nasi D., di Somma L., Gladi M., Moriconi E., Scerrati M., Iacoangeli M., Dobran M. New or Blossoming Hemorrhagic Contusions After Decompressive Craniectomy in Traumatic Brain Injury: Analysis of Risk Factors. Front Neurol. 2019. 9. 1186. doi: 10.3389/fneur.2018.01186.

6. Emami P., Czorlich P., Fritzsche F.S., Westphal M., Rueger J.M., Lefering R., Hoffmann M. Impact of Glasgow Coma Scale score and pupil parameters on mortality rate and outcome in pediatric and adult severe traumatic brain injury: a retrospective, multicenter cohort study. J Neurosurg. 2017. 126(3). 760-767. doi: 10.3171/2016.1.JNS152385.

7. Jha R.M., Elmer J., Zusman B.E., Desai S., Puccio A.M., Okonkwo D.O. et al. Intracranial pressure trajectories: A novel approach to informing severe traumatic brain injury phenotypes. Crit. Care Med. 2018. 46(11). 1792–1802. doi: 10.1097/CCM.0000000000003361.

8. Zeiler F.A., McFadyen C., Newcombe V.F.J., Synnot A., Donoghue E.L., Ripatti S. et al. Genetic influences on patient-oriented outcomes in traumatic brain injury: A living systematic review of non-apolipoprotein E single-nucleotide polymorphisms. J. Neurotrauma. 2021. 38(8). 1107- 1123. doi: 10.1089/neu.2017.5583.

9. Zeiler F.A., Thelin E.P., Donnelly J., Stevens A.R., Smielewski P., Czosnyka M. et al. Genetic drivers of cerebral blood flow dysfunction in TBI: A speculative synthesis. Nat. Rev. Neurol. 2019. 15. 25–39. doi: 10.1038/s41582-018-0105-9.

10. McFadyen C.A., Zeiler F.A., Newcombe V., Synnot A., Steyerberg E., Gruen R.L. et al. Apolipoprotein E4 polymorphism and outcomes from traumatic brain injury: A living systematic review and meta-analysis. J. Neurotrauma. 2021. 38(8). 1124-1136. doi: 10.1089/neu.2018.6052.

11. Neurosurgery and neuroreanimatology / edited by V.V. Krylov. Moscow: ABV-press. 2018. 783. in Russian.

12. Alshogran O.Y., Al-Delaimy W.K. Understanding of international committee of medical journal editors authorship criteria among faculty members of pharmacy and other health sciences in Jordan. J Empir Res Hum Res Ethics. 2018. 13(3). 276-284. doi: 10.1177/1556264618764575.

13. Lang T.A., Altman D.G. Statistical analyses and methods in the published literature: The SAMPL guidelines. Medical Writing. 2016. 25(3). 31–6. doi: 10.18243/eon/2016.9.7.4.

14. Lisianyi N.I. The dual role of the immune system in the pathogenesis of traumatic brain injury. Ukrainian Neurosurgical Journal. 2019. 25(1). 5-11. doi: 10.25305/unj.155107.