Novel insights into immune dysregulation and cytokine signatures in intensive care settings: bridging IL-6, IL-10, TNF-α to endothelial, hepatic, and hematological dysfunction in severe dengue, a schematic meta-analysis.
Abstract
Background & objective: Severe dengue is a global health concern and immune dysregulation is a key contributor to its pathogenesis. The aim of this schematic review was to review the association of the cytokine biomarkers mainly interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in immune dysregulation among patients suffering from severe dengue.
Methodology: The review followed PRISMA 2020 guidelines. The literature was searched from PubMed, Scopus, Web of Science, and Google Scholar up to August 2025. Qualified studies included those which measured IL-6, IL-10 or TNF- α in confirmed dengue patient. Meta-analysis was performed to assess standardized mean differences (SMDs) for key cytokines. The risk of bias was determined using Newcastle-Ottawa Scale and the GRADE approach was applied for certainty of evidence.
Results: Higher levels were observed, of IL-6 and IL-10 in severe dengue, and TNF-α with late complications in this study. Meta-analysis correlated high levels of cytokines with severe dengue IL-6 (SMD = 16.79, 95% CI = -15.25-48.84), IL-10 (SMD = 0.13, 95%CI = -0.37-0.63) and TNF-α (SMD = 0.53, 95% CI = 0.25-0.82). The evidence confidence was moderate and high by IL-6 and IL-10 and high in TNF-α respectively.
Conclusion: The levels of IL-6 and IL-10 were significantly high in severe dengue cases, but heterogeneity across studies reduced the prognostic integrity. TNF-α emerged as a potent indicator of mild and severe dengue. To establish the clinical uses of these biomarkers as a risk-stratifying tool, standardized, multicentric studies are needed to validate these findings.
Abbreviations: DF: dengue fever, DHF: dengue hemorrhagic fever, DSS: dengue shock syndrome, IL-6: Interleukin-6, IL-10: Interleukin-10, SMD: standardized mean differences, TNF-α: tumor necrosis factor-alpha
Keywords: Dengue Hemorrhagic Fever (DHF), Cytokine Storm, Biomarkers, Cytokines, IL-6, IL-10, TNF-α
Citation: Bukhari AAS, Devi D, Minhas M, Noureen A, Javed H, Zaidi SIA, Khaliq H. Novel insights into immune dysregulation and cytokine signatures in intensive care settings: bridging IL-6, IL-10, TNF-α to endothelial, hepatic, and hematological dysfunction in severe dengue, a schematic meta-analysis. Anaesth. pain intensive care 2025;29(8):1022-1031. DOI: 10.35975/apic.v29i8.3039
Received: October 16, 2025; Revised: October 18, 2025; Accepted: October 18, 2025
