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Updated: Jul 19, 2026
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity
Emer Ryan1,2,3,4, Lynne Kelly1,2,3, Catherine Stacey1,2,3
1Department of Paediatrics, Trinity College, The University of Dublin, Dublin, Ireland.
Insights
Pediatric traumatic brain injury (TBI) alters immune responses, with suppressed cytokine profiles in mild TBI (mTBI) persisting post-injury. Severe TBI (sTBI) shows increased immune activation, particularly after endotoxin stimulation, indicating varied immune dysfunction.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Pediatric traumatic brain injury (TBI) can lead to lasting neurocognitive deficits.
- Childhood head injuries are common, with variable recovery outcomes.
- Immune system activation and altered cytokine levels are observed post-TBI, potentially differing from adult responses.
Purpose of the Study:
- To investigate immune system alterations in children following TBI.
- To compare cytokine profiles and endotoxin responses in mild TBI (mTBI) and severe TBI (sTBI) patients versus healthy controls.
Main Methods:
- Examined pro- and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ) in whole blood.
- Measured cytokines at baseline and after in vitro endotoxin stimulation.
- Included children with sTBI (GCS ≤ 8), mTBI (GCS 14/15) at 0-4 days and 10-14 days post-injury, and healthy controls.
Main Results:
- 208 children (110 TBI, 98 controls) were enrolled; 104 had mTBI, 6 had sTBI.
- Children with TBI showed elevated baseline IL-6; mTBI had increased IFN-γ, while sTBI had decreased IFN-γ.
- mTBI exhibited altered baseline cytokine profiles (decreased IL-8, IL-10, IL-17A, TNF-α) persisting for 2 weeks, with heightened endotoxin-induced IL-8 and TNF-α responses.
- A predictive model for mTBI using the IL-6/IL-10 ratio achieved an AUC of 0.801.
Conclusions:
- All pediatric TBI cases, including mTBI, demonstrate altered cytokine profiles and immune responses to endotoxin.
- mTBI cases showed suppressed cytokine responses to endotoxin and persistent immune dysfunction.
- sTBI cases exhibited increased immune activation, particularly following endotoxin challenge.
Background:
Paediatric traumatic brain injury (TBI) is recognised to have significant longer-term neurocognitive effects. Childhood is a time of high risk for head injury. Functional recovery is variable with a combination of any or all of physical, cognitive and emotional impairment. Immune activation and alteration in cytokine levels are present following TBI which may differ from adults.
Methods:
Pro- and anti-inflammatory cytokines including Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-17A, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were examined at baseline and following in vitro treatment with endotoxin of whole blood, in the following children: severe TBI (sTBI: initial Glasgow coma scale(GCS) ≤ 8), mild TBI (mTBI; GCS 14/15) at 0-4d and at 10-14d post-TBI and compared to healthy age-matched controls.
Results:
The study enrolled 208 children, including 110 with TBI cohort (n = 104 mild; 6 severe) and controls (n = 98). At baseline all children with TBI had increased IL-6. The mTBI group had significantly increased IFN-γ versus controls. In sTBI at baseline, IFN-γ was decreased compared to controls. At baseline IL-8, IL-10, IL-17A, and TNF-α were decreased in mTBI compared to controls. This persisted at 2 week post-mTBI. The AUC for detecting mTBI was 0.801 CI (0.73-086) using IL6/IL10 ratio. mTBI showed a greater fold change in IL-8 and TNF-α in response to endotoxin stimulation, a response that persisted at 2 weeks. Children with sTBI did not have a significant IL-6 response to endotoxin, but did show an increase in IL-17A.
Conclusion:
Children with all TBI including mTBI show altered cytokine profiles and altered endotoxin responses. Although cytokines increased in sTBI especially in response to endotoxin, suppressed responses were found in mTBI coupled with persistent immune dysfunction post-injury.
