The significance of Cerebrospinal fluid/Serum ratios of interleukins-6, -8, -10 in the differential diagnosis of meningitis in children
https://doi.org/10.21508/1027-4065-2026-71-2-66-77
Abstract
Meningitis is a devastating disease for which appropriate initial treatment improves outcome. Management strategies are based on the etiology, which is most commonly bacterial or viral. However, prompt detection of the etiologic agent is not possible in all cases; therefore, the investigation of additional early differential diagnostic markers, such as interleukins, remains relevant.
The aim of the study. To determine the differential diagnostic value of cerebrospinal fluid/serum ratios of interleukins 6, 8, 10 in purulent bacterial and viral meningitis in children.
Materials and Methods. This prospective study enrolled 63 children, divided into three groups: bacterial meningitis (n=20), viral meningitis (n=17), and a control group (n=26). Concentrations of albumin, interleukins 6, 8, 10 were evaluated in cerebrospinal fluid and serum samples obtained in parallel on the day of admission. Cerebrospinal fluid/serum ratios (QAlb and QIL) were calculated. Receiver operating characteristic (ROC) curve analysis was performed with estimation of the area under the curve (AUC) and determination of optimal cut-off values. A predictive model was developed with binary logistic regression.
Results. Interleukin 6 concentrations in cerebrospinal fluid (AUC = 0.982) and serum (AUC = 0.991), serum interleukin 10 (AUC = 0.965), and QIL10 (AUC = 0.953; sensitivity = 95.0%, specificity = 76.5%) demonstrated high diagnostic accuracy in differentiating bacterial from viral meningitis. Combining QAlb and QIL10 in the predictive model equation increased sensitivity (100%) and specificity (88.2%). A possible mechanism of intrathecal regulation of inflammation in the early stages of meningitis is proposed. In bacterial meningitis, only pro-inflammatory interleukins 6 and 8 are synthesized intrathecally, resulting in neutrophilic pleocytosis. In viral meningitis, intrathecal production of interleukins 6 and 8 and anti-inflammatory interleukin 10 inhibiting neutrophil recruitment into the cerebrospinal fluid leads to mixed or lymphocytic pleocytosis.
Conclusion. Evaluation of interleukin 6 concentration in cerebrospinal fluid and application of the predictive formula incorporating QAlb and QIL10 enables differentiation between bacterial and viral meningitis at the early stages of the disease.
About the Authors
A. M. DeomkinaRussian Federation
117997, Moscow
R. F. Sayfullin
Russian Federation
117997, Moscow
107031, Moscow
A. K. Shakaryan
Russian Federation
117997, Moscow
108819, Moscow
125310, Moscow
G. D. Guseva
Russian Federation
125310, Moscow
T. V. Gorkov
Russian Federation
125310, Moscow
O. V. Shamsheva
Russian Federation
117997, Moscow
References
1. Skar G., Flannigan L., Latch R., Snowden J. Meningitis in Children: Still a Can’t-Miss Diagnosis. Pediatr Rev. 2024; 45(6): 305–315. DOI: 10.1542/pir.2023-006013
2. van de Beek D., Cabellos C., Dzupova O., Esposito S., Klein M., Kloek A.T. et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect. 2016; 22 Suppl 3: S37-S62. DOI: 10.1016/j.cmi.2016.01.007
3. Ivaska L., Herberg J., Sadarangani M. Distinguishing community-acquired bacterial and viral meningitis: Microbes and biomarkers. J Infect. 2024; 88(3): 106–111. DOI: 10.1016/j.jinf.2024.01.010
4. Groeneveld N.S., Bijlsma M.W., van de Beek D., Brouwer M.C. Biomarkers in paediatric bacterial meningitis: a systematic review and meta-analysis of diagnostic test accuracy. Clin Microbiol Infect. 2025; 31(5): 702–712. DOI: 10.1016/j.cmi.2024.12.009
5. Kalchev Y., Argirova P., Boev I., Yaneva A., Vatev N., Stoycheva M. et al. Cytokine profile in patients with acute bacterial meningitis. Cytokine. 2023; 170:156315. DOI: 10.1016/j.cyto.2023.156315
6. Pinto Junior V.L., Rebelo M.C., Gomes R.N., Assis E.F., Castro-Faria-Neto H.C., Bóia M.N. IL-6 and IL-8 in cerebrospinal fluid from patients with aseptic meningitis and bacterial meningitis: their potential role as a marker for differential diagnosis. Braz J Infect Dis. 2011; 15(2): 156–158. DOI: 10.1590/s1413-86702011000200011
7. Reiber H. Liquordiagnostik in der Neurologie: Paradigmenwechsel bei Hirn-Schranken, Immunsystem und chronischen Krankheiten (essentials). Berlin; Springer, 2023; 75. DOI: 10.1007/978-3-662-68136-7
8. Reiber H., Peter J.B. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001; 184(2): 101–122. DOI: 10.1016/s0022-510x(00)00501-3
9. Zimmermann K., Kühn H.-J., Linke E. Praanalytik. ̈ Praktische Liquordiagnostik in Frage und Antwort. Düsseldorf, 2014; 10–18
10. Sullivan M.A., Lane S.D., McKenzie A.D.J., Ball S.R., Sunde M., Neely G.G. et al. iPSC-derived PSEN2 (N141I) astrocytes and microglia exhibit a primed inflammatory phenotype. J Neuroinflammation. 2024; 21(1): 7. DOI: 10.1186/s12974-023-02951-2
11. Strle K., Zhou J.H., Shen W.H., Broussard S.R., Johnson R.W., Freund G.G. et al. Interleukin-10 in the brain. Crit Rev Immunol. 2001; 21(5): 427–449.
12. Deomkina A.M., Sayfullin R.F., Shakaryan A.K., Shamsheva O.V. CSF/serum ratios: modern approach to assess intrathecal response. Infekciya i immunitet 2025; 15(4): 625–634. (in Russ.). DOI: 10.15789/2220-7619-CSR-17927
13. Ausgewählte Methoden der Liquordiagnostik und Klinischen Neurochemie. Germany: Deutsche Gesellschaft für Liquordiagnostik und Klinische Neurochemie e.V. 2020; 100 p. https://www.dgln.de/methodenkatalog
14. ARUP Laboratories. Cytokine Panel 13, CSF. https://www.aruplab.com/Testing-Information/resources/HotLines/HotLineDocs/Feb2021/3003259.pdf. Ссылка активна на 22.01.2026
15. Caragheorgheopol R., Țucureanu C., Lazăr V., Florescu S.A., Lazăr D.S., Caraş I. Cerebrospinal fluid cytokines and chemokines exhibit distinct profiles in bacterial meningitis and viral meningitis. Exp Ther Med. 2023; 25(5): 204. DOI: 10.3892/etm.2023.11903
16. StatTech. Онлайн-калькуляторы статистических расчетов размера выборки. https://stattech.ru/calculators. Ссылка активна на 22.01.2026
17. Cohen J.F., Korevaar D.A., Altman D.G., Bruns D.E., Gatsonis C.A., Hooft L. et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016; 6(11): e012799. DOI: 10.1136/bmjopen-2016-012799
18. Olie S.E., Staal S.L., Ter Horst L., van Zeggeren I.E., Man W.K., Tanck M.W.T. et al. Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections. J Infect. 2024; 88(3): 106–117. DOI: 10.1016/j.jinf.2024.01.016
19. Tan C.D., van den Broek B., Womersley R.S., Kaforou M., Hagedoorn N.N., van der Flier M. et al. A Novel Combination of Host Protein Biomarkers to Distinguish Bacterial From Viral Infections in Febrile Children in Emergency Care. Pediatr Infect Dis J. 2023; 42(7): e235-e242. DOI: 10.1097/INF.0000000000003952
20. Erta M., Quintana A., Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci. 2012; 8(9): 1254–1266. DOI: 10.7150/ijbs.4679
21. Matsushima K., Yang D., Oppenheim J.J. Interleukin-8: An evolving chemokine. Cytokine. 2022; 153: 155828. DOI: 10.1016/j.cyto.2022.155828
22. Patilas C., Varsamos I., Galanis A., Vavourakis M., Zachariou D., Marougklianis V. et al. The Role of Interleukin-10 in the Pathogenesis and Treatment of a Spinal Cord Injury. Diagnostics (Basel). 2024; 14(2): 151. DOI: 10.3390/diagnostics14020151
Review
For citations:
Deomkina A.M., Sayfullin R.F., Shakaryan A.K., Guseva G.D., Gorkov T.V., Shamsheva O.V. The significance of Cerebrospinal fluid/Serum ratios of interleukins-6, -8, -10 in the differential diagnosis of meningitis in children. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2026;71(2):66-77. (In Russ.) https://doi.org/10.21508/1027-4065-2026-71-2-66-77
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