DOI: https://doi.org/10.14710/jai.v0i0.82097

Prognostic Value of IL-6 for Mortality in ICU Patients with Sepsis: A Systematic Review and Meta-Analysis

1Department of Biomedic, Faculty of Medicine, Universitas Yarsi, Jakarta, Indonesia

2Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Diponegoro/RSUP Dr.Kariadi, Semarang, Indonesia

Received: 30 Jan 2026; Revised: 23 Apr 2026; Accepted: 24 Apr 2026; Available online: 24 Apr 2026; Published: 31 Jul 2026.
Open Access Copyright 2026 JAI (Jurnal Anestesiologi Indonesia)
Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License.

Citation Format:
Cover Image
Abstract

Objectives: To evaluate the prognostic value of interleukin-6 (IL-6) for mortality in intensive care unit (ICU) patients with sepsis.

Study design: This study was conducted as a systematic review and meta-analysis of observational studies. Study quality was assessed using the Quality in Prognosis Studies (QUIPS) tool, and adjusted hazard ratios (HRs) were pooled using a random-effects model.

Data sources: A comprehensive literature search was performed in PubMed, Scopus, Cochrane Library, and ScienceDirect for studies published up to March 2026. Reference lists of relevant articles were also screened to identify additional eligible studies.

Data synthesis: Eighteen studies were included in the qualitative synthesis, and six studies were included in the meta-analysis. Elevated IL-6 levels were consistently higher in non-survivors across studies. The pooled analysis demonstrated that increased IL-6 levels were significantly associated with higher mortality risk (HR = 1.39, 95% CI 1.14–1.70; p = 0.001), with moderate heterogeneity (I² = 70%), likely reflecting differences in study populations, measurement timing, and study design. Sensitivity analysis excluding one large multicenter study reduced heterogeneity (I² = 0%) while maintaining statistical significance (HR = 1.29, 95% CI 1.13–1.47; p < 0.001), confirming the robustness of the findings.

Conclusions: Elevated IL-6 is significantly associated with increased mortality in ICU patients with sepsis. Despite heterogeneity, the findings are consistent and support the role of IL-6 as a prognostic biomarker, particularly when integrated with other clinical and laboratory parameters.

Registration: The protocol for this systematic review was prospectively registered in PROSPERO.

Fulltext View|Download Email colleagues
Keywords: intensive care unit; interleukin-6; mortality; prognosis; sepsis

Article Metrics:

Article Info
Section: Systematic Reviews
Language : EN
Most cited articles
Midazolam Intravena Dosis Rendah Tidak Mempengaruhi Nitric Oxide Intraperitoneal Mencit Balb/C Yang Terpapar Lipopolisakarida Patofisiologi Penyakit Jantung Koroner More cited articles
  1. Ziesmann MT, Marshall JC. Multiple Organ Dysfunction: The Defining Syndrome of Sepsis. Surg Infect (Larchmt) 2018;19(2):184–190; doi: 10.1089/SUR.2017.298;WEBSITE:WEBSITE:SAGE;WGROUP:STRING:PUBLICATION
  2. Moor M, Rieck B, Horn M, et al. Early Prediction of Sepsis in the ICU Using Machine Learning: A Systematic Review. Front Med (Lausanne) 2021;8:607952; doi: 10.3389/FMED.2021.607952/TEXT
  3. Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci 2013;50(1):23–36; doi: 10.3109/10408363.2013.764490
  4. Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nature Reviews Rheumatology 2017 13:7 2017;13(7):399–409; doi: 10.1038/nrrheum.2017.83
  5. Sygitowicz G, Sitkiewicz D. Molecular mechanisms of organ damage in sepsis: an overview. The Brazilian Journal of Infectious Diseases 2020;24(6):552–560; doi: 10.1016/J.BJID.2020.09.004
  6. Jiang Y, Jiang FQ, Kong F, et al. Inflammatory anemia-associated parameters are related to 28-day mortality in patients with sepsis admitted to the ICU: a preliminary observational study. Ann Intensive Care 2019;9(1); doi: 10.1186/S13613-019-0542-7
  7. Liu J, Bai C, Li B, et al. Mortality prediction using a novel combination of biomarkers in the first day of sepsis in intensive care units. Sci Rep 2021;11(1); doi: 10.1038/S41598-020-79843-5
  8. Costa RT, de Araújo OR, Brunialti MKC, et al. T helper type cytokines in sepsis: time-shared variance and correlation with organ dysfunction and hospital mortality. Braz J Infect Dis 2019;23(2):79–85; doi: 10.1016/J.BJID.2019.04.008
  9. Picod A, Morisson L, de Roquetaillade C, et al. Systemic Inflammation Evaluated by Interleukin-6 or C-Reactive Protein in Critically Ill Patients: Results From the FROG-ICU Study. Front Immunol 2022;13:868348; doi: 10.3389/FIMMU.2022.868348/TEXT
  10. Siddiqui S, Gurung RL, Liu S, et al. Genetic Polymorphisms and Cytokine Profile of Different Ethnicities inSeptic Shock Patients and their Association with Mortality. Indian J Crit Care Med 2019;23(3):135–138; doi: 10.5005/JP-JOURNALS-10071-23136
  11. Karampela I, Kounatidis D, Vallianou NG, et al. Kinetics of the Lactate to Albumin Ratio in New Onset Sepsis: Prognostic Implications. Diagnostics (Basel) 2024;14(17); doi: 10.3390/DIAGNOSTICS14171988
  12. Chen L, Lin X, Yu X, et al. Decoy receptor 3 as a prognostic biomarker for sepsis and septic shock according to the Sepsis-3 definitions. Front Cell Infect Microbiol 2025;15:1529917; doi: 10.3389/FCIMB.2025.1529917/TEXT
  13. Karampela I, Christodoulatos GS, Vallianou N, et al. Circulating Chemerin and Its Kinetics May Be a Useful Diagnostic and Prognostic Biomarker in Critically Ill Patients with Sepsis: A Prospective Study. Biomolecules 2022;12(2); doi: 10.3390/BIOM12020301
  14. Shimazui T, Oami T, Shimada T, et al. Age-dependent differences in the association between blood interleukin-6 levels and mortality in patients with sepsis: a retrospective observational study. J Intensive Care 2025;13(1); doi: 10.1186/S40560-025-00775-1
  15. Aktaş F, Zer Y, Elay G, et al. First Signs at Admission: Prognostic Value of Initial Proinflammatory Markers for Sepsis and Mortality in ICU Patients. Pathogens 2025;14(9):907; doi: 10.3390/PATHOGENS14090907/S1
  16. Ameen SS, Hegde S, Parida A, et al. Interleukin-6 as a biomarker of sepsis and its clinical utility in predicting mortality: a prospective observational study. J Infect Dev Ctries 2025;19(10):1470–1478; doi: 10.3855/JIDC.20800
  17. Gamarra-Morales Y, Molina-López J, Santiago-Ruiz FC, et al. Efficiency of IL-6 in Early Prognosis and Follow-Up in Critically Ill Patients with Septic Shock. Diseases 2024;12(11); doi: 10.3390/DISEASES12110298
  18. Jiang J, Huang H, Li H, et al. Sepsis-related coagulation-inflammation score: Development and validation for predicting 28-day mortality in patients with sepsis. Thromb Res 2025;255; doi: 10.1016/J.THROMRES.2025.109479
  19. Khan SH, Perkins AJ, Eltarras AM, et al. Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study. PLoS One 2023;18(9); doi: 10.1371/JOURNAL.PONE.0290298
  20. Lei W, Ren Z, Su J, et al. Immunological risk factors for sepsis-associated delirium and mortality in ICU patients. Front Immunol 2022;13:940779; doi: 10.3389/FIMMU.2022.940779/TEXT
  21. Ríos-Toro JJ, Márquez-Coello M, García-Álvarez JM, et al. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock. PLoS One 2017;12(4); doi: 10.1371/JOURNAL.PONE.0175254
  22. Tsai YH, Hung KY, Fang WF. Leptin and Iinterlukin-6 relationship and influence of mortality in sepsis. BMC Infect Dis 2025;25(1); doi: 10.1186/S12879-025-10829-2
  23. Chen HP, Wang XY, Pan XY, et al. Circulating Neutrophil-Derived Microparticles Associated with the Prognosis of Patients with Sepsis. J Inflamm Res 2020;13:1113–1124; doi: 10.2147/JIR.S287256
  24. Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med 2013;158(4):280–286; doi: 10.7326/0003-4819-158-4-201302190-00009

Last update:

No citation recorded.

Last update: 2026-07-21 05:41:47

No citation recorded.