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Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study

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European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1–4) or unfavorable (5–8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL‐1β, IL‐2, IL‐4, IL‐10, IL‐12p70, IL‐17A, IFN‐γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines.

Conclusion: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes.

Trial registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022.

What is Known:

• Inflammation is an important secondary physiological response to TBI.

What is New:

• The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

AUC:

Area under curve

CI:

Confidence interval

GCS:

Glasgow Coma Scale

GOS-E Peds:

Glasgow Outcome Scale Extended Pediatrics

IFN:

Interferon

IL:

Interleukin

IQR:

Interquartile range

m-sTBI:

Moderate to severe traumatic brain injury

mTBI:

Moderate traumatic brain injury

PTS:

Pediatric Trauma Score

ROC:

Receiver operating characteristic

sTBI:

Severe traumatic brain injury

TBI:

Traumatic brain injury

TNF:

Tumor necrosis factor

WBC:

White blood cell

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Acknowledgements

We would like to acknowledge the patients and parents who participated in this study and the nurses who drew blood samples.

Funding

This work was supported by the Natural Science Foundation Project of Chongqing of China (cstc2020jcyj-msxmX1087) and the Program for Youth Innovation in Future Medicine from Chongqing Medical University: Basic and Clinical Study of Critical Illness in Children (2021-W0111).

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Author notes

  1. Haixin Huang and Guo Fu are co-first authorship.

Authors and Affiliations

  1. Department of Critical Care Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Haixin Huang, Siwei Lu, Song Chen, Junming Huo, Yunni Ran, Changxue Xiao, Jian Chen, Dandan Pi, Fang Zhou, Hongxing Dang, Chengjun Liu & Yue-qiang Fu

  2. Center for Clinical Molecular Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Guo Fu

  3. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, China

    Haixin Huang, Guo Fu, Siwei Lu, Song Chen, Junming Huo, Yunni Ran, Changxue Xiao, Jian Chen, Dandan Pi, Fang Zhou, Hongxing Dang, Chengjun Liu & Yue-qiang Fu

  4. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China

    Haixin Huang, Guo Fu, Siwei Lu, Song Chen, Junming Huo, Yunni Ran, Changxue Xiao, Jian Chen, Dandan Pi, Fang Zhou, Hongxing Dang, Chengjun Liu & Yue-qiang Fu

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Contributions

YF designed, supervised and revised the paper. HH contributed to the data collection, data analysis, literature search, table, figures design and writing. GF contributed to cytokines detection and writing. SL, SC, JH, YR, CX, JC and FZ participated in sample acquisition and data collection. DP, CL and HD participated in the database management and statistical analysis. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Yue-qiang Fu.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Institutional Ethics Review Board of the Chongqing Medical University Children's Hospital (Approval Number: 2020-239-2). Informed consent was obtained from the patients and/or their parents.

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Not applicable.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Communicated by Gregorio Milani

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Huang, H., Fu, G., Lu, S. et al. Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05604-5

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