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

Cytokine-Mediated Systemic Inflammation in Patient with Sepsis in ICU: A Systematic Literature Review and Meta- Analysis of Interleukin-6 and Tumor Necrosis -

1Program Studi Sains Biomedis, Program Doktor Sekolah Pascasarjana, Fakultas Kedokteran Yarsi, Jakarta, Indonesia

2Departemen Anestesiologi dan Terapi Intensif, Fakultas kedokteran, Universitas Diponegoro/RSUP Dr. Kariadi, Semarang, Indonesia

Received: 30 Jan 2026; Revised: 23 Apr 2026; Accepted: 24 Apr 2026; Available online: 24 Apr 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.

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Abstract

ABSTRACT

Objectives: To systematically evaluate and quantify the prognostic value of circulating interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels for mortality and disease severity in adult intensive care unit (ICU) patients with sepsis.

Study design: This study was conducted as a systematic review and meta-analysis of observational studies and randomized controlled trials. Evidence quality was assessed using the Newcastle–Ottawa Scale for observational studies. Quantitative synthesis was performed using meta-analytic techniques.

Data sources: A comprehensive literature search was performed in PubMed, Scopus, Web of Science, and Embase from database inception to the most recent available date. Reference lists of relevant articles were also manually screened to identify additional eligible studies.

Data synthesis: Two studies evaluating IL-6 (196 ICU sepsis patients) demonstrated significantly higher IL-6 levels in non-survivors compared with survivors, with a large and consistent pooled effect size (SMD −1.92; 95% CI −2.27 to −1.57) and no interstudy heterogeneity, supporting IL-6 as a robust prognostic biomarker. TNF-α data from two studies (270 patients) also showed significantly elevated levels in non-survivors (SMD −2.70; 95% CI −3.05 to −2.35); however, substantial heterogeneity and slight funnel plot asymmetry reduced the certainty and generalizability of its prognostic value.

Conclusions: Elevated IL-6 and TNF-α levels are associated with increased mortality in ICU patients with sepsis. IL-6 demonstrates more consistent and reliable prognostic performance, supporting its use for early risk stratification in critical care, whereas TNF-α may serve as a complementary biomarker.

Registration: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Prospective registration in the PROSPERO database.

Keywords:
interleukin-6; intensive care unit; mortality; sepsis; tumor necrosis factor-α

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Keywords: interleukin-6; intensive care unit; mortality; sepsis; tumor necrosis factor-α

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Section: Systematic Reviews
Language : EN
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