# Potential Role of Serum Cytokines and Chemokines as Biomarkers of Injury Severity and Functional Outcomes Following Pediatric Traumatic Brain Injury

**Authors:** Kathryn Swaby, Alexander J. Skirvin, Natalie Machado, Maria Mateo Chavez, Julia Alexis Bernal, Ana Fuentes, Charlene P. Pringle, Kourtney Guthrie, Jennifer Coto, Rajderkar Dhanashree, Joslyn Gober, Paula Karina Perez, Juan P. Solano, Heather J. McCrea, Ricardo Loor-Torres, Joyce Kaufman, Ayham Alkhachroum, Kristine H. O’Phelan, Firas Kobeissy, Robert W. Keane, Kevin K. Wang, W. Dalton Dietrich, Juan Pablo de Rivero Vaccari, Jennifer C. Munoz Pareja

PMC · DOI: 10.3390/cells15010019 · Cells · 2025-12-22

## TL;DR

This study explores how blood cytokines could help assess the severity and outcomes of traumatic brain injuries in children.

## Contribution

The study identifies specific cytokines that may serve as potential biomarkers for pediatric TBI severity and prognosis.

## Key findings

- Elevated IL-6 and IL-10 levels at enrollment were strongly associated with severe TBI.
- Cytokines like IL-6, IL-10, and IL-16 showed potential as biomarkers for TBI outcomes.
- Several inflammatory markers were found to be significantly altered in children with TBI compared to controls.

## Abstract

What are the main findings?
Cytokines may be beneficial as biomarkers of pediatric TBI severity and prognosis

Cytokines may be beneficial as biomarkers of pediatric TBI severity and prognosis

What are the implications of the main findings?
Additional studies may be beneficial in delineating the role of cytokines in assessing pediatric TBI.

Additional studies may be beneficial in delineating the role of cytokines in assessing pediatric TBI.

Traumatic brain injury (TBI) is one of the leading causes of death and neurological disability worldwide. The search for biomarkers that indicate TBI severity and prognosis with greater accuracy is ongoing. This study aimed to evaluate the significance of several neuroinflammatory cytokines and chemokines, assessing their potential as biomarkers in pediatric TBI (pTBI). This was an exploratory analysis of inflammatory cytokines and chemokines measured in a subset of 26 children aged 0–18 years with TBI and 21 controls. TBI severity was determined by GCS. The functional outcome was measured via the GOS-E score at 6 weeks and 3, 6, 9, and 12 months post-injury. Serum samples were analyzed for ICAM-1, VCAM-1, SAA, CRP, IFN-g, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8, TNF-a, TNF-b, eotaxin, eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1a, MIP-1b and TARC. Levels of IL-6, IL-10, IL-13, IL-16, MDC, and GM-CSF were increased, and IFN-γ, IL-5, IL-8, and eotaxin-3 were decreased at enrollment when compared with controls. Elevated IL-6 and IL-10 at enrollment were associated with severe TBI (AUC of 1, p = 0.0002 and p = <0.0001, respectively). IL-6, IL-10, IL-16, and TNF-β at enrollment and IL-5 at 24 h were elevated in children with unfavorable outcomes, with an AUC > 0.8, suggesting biomarker potential. Our data indicate that several cytokines and chemokines measured after TBI may aid in the assessment of pTBI severity and prognosis. IL-6, IL-10, and IL-16 may show potential as biomarkers for pTBI severity and outcomes.

## Linked entities

- **Proteins:** IL6 (interleukin 6), IL10 (interleukin 10), IL13 (interleukin 13), IL16 (interleukin 16), ADAM11 (ADAM metallopeptidase domain 11), CSF2 (colony stimulating factor 2), IFNG (interferon gamma), IL5 (interleukin 5), CXCL8 (C-X-C motif chemokine ligand 8), LTA (lymphotoxin alpha)
- **Diseases:** traumatic brain injury (MONDO:0858950)

## Full-text entities

- **Genes:** IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, IL16 (interleukin 16) [NCBI Gene 3603] {aka LCF, NIL16, PRIL16, prIL-16}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, CCL26 (C-C motif chemokine ligand 26) [NCBI Gene 10344] {aka IMAC, MIP-4a, MIP-4alpha, SCYA26, TSC-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SAA [NCBI Gene 6287], CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357] {aka CKb10, MCP-4, NCC-1, NCC1, SCYA13, SCYL1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, CCL22 (C-C motif chemokine ligand 22) [NCBI Gene 6367] {aka A-152E5.1, ABCD-1, DC/B-CK, MDC, SCYA22, STCP-1}, LTA (lymphotoxin alpha) [NCBI Gene 4049] {aka LT, TNFB, TNFSF1, TNLG1E}, CCL17 (C-C motif chemokine ligand 17) [NCBI Gene 6361] {aka A-152E5.3, ABCD-2, SCYA17, TARC}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}
- **Diseases:** inflammatory (MESH:D007249), death (MESH:D003643), TBI (MESH:D000070642), neurological disability (MESH:D009069), Injury (MESH:D014947), neuroinflammatory cytokines (MESH:D000090862)

## Full text

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## Figures

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## References

62 references — full list in the complete paper: https://tomesphere.com/paper/PMC12784923/full.md

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Source: https://tomesphere.com/paper/PMC12784923