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Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children
M J Bell1, P M Kochanek, L A Doughty
1Department of Anesthesiology and Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania 15260, USA.
Insights
This study found elevated levels of both pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10) in the cerebrospinal fluid (CSF) of children following severe traumatic brain injury (TBI). Increased IL-10 was linked to younger age and mortality in pediatric TBI patients.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Cytokines, such as interleukin-6 (IL-6) and interleukin-10 (IL-10), are implicated in the pathophysiology of traumatic brain injury (TBI).
- IL-6 is a pro-inflammatory cytokine involved in central nervous system (CNS) regeneration, while IL-10 is anti-inflammatory.
- Elevated cytokine levels in cerebrospinal fluid (CSF) and serum are indicators of inflammation in various pediatric neurological conditions.
Purpose of the Study:
- To investigate the concentrations of IL-6 and IL-10 in the CSF of children with severe TBI.
- To determine if IL-6 and IL-10 levels correlate with clinical factors such as age and mortality in pediatric TBI.
- To establish baseline cytokine levels in pediatric TBI for comparison with control groups.
Main Methods:
- Analysis of CSF samples from 15 children with severe TBI (Glasgow Coma Scale [GCS] ≤ 7) collected within the first 3 days post-injury.
- Quantification of IL-6 and IL-10 concentrations using enzyme-linked immunosorbent assay (ELISA).
- Comparison of cytokine levels with a control group of 20 children without CNS inflammation.
Main Results:
- CSF IL-6 levels were significantly elevated in TBI patients compared to controls on all measured days (p < 0.0001).
- CSF IL-10 levels were also significantly increased in TBI patients versus controls (p < 0.01).
- Higher IL-10 concentrations were independently associated with younger age (< 4 years) and increased mortality (p = 0.004 and p = 0.04, respectively).
Conclusions:
- This study confirms elevated IL-6 in pediatric TBI CSF, consistent with adult findings.
- It is the first study to demonstrate increased IL-10 in human CSF following TBI.
- Findings suggest a potential age-dependent production of IL-10 in pediatric TBI and its association with clinical outcomes.
Abstract:
Cytokines may play an important role in the pathophysiology of traumatic brain injury (TBI) in children. Interleukin-6 (IL-6) is a proinflammatory cyotkine that plays a role in regenerative processes within the central nervous system (CNS), whereas interleukin-10 (IL-10) is an antiinflammatory cytokine. Both have been measured in serum and cerebrospinal fluid (CSF) as an index of the degree of inflammation in diseases, including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the CSF of children after severe TBI. Fifteen children who sustained severe TBI (Glascow Coma Score [GCS] < or = 7) were studied. Standard neurointensive care was provided. Ventricular CSF collected the first 3 days after TBI was analyzed for IL-6 and IL-10 concentrations by ELISA. Controls were 20 children who were evaluated for meningitis with diagnostic lumbar puncture subsequently found to have no CSF pleocytosis and negative cultures. IL-6 was increased in children after TBI versus controls on all days studied (day 1, 3158.2 +/- 621.8 pg/ml; day 2, 1111.6 +/- 337.0 pg/ml; day 3, 826.7 +/- 193.5 pg/ml vs. 20.6 +/- 5.8 pg/ml, p < 0.0001, Mann-Whitney Rank Sum). IL-10 was increased in children after TBI vs controls on all days studied (day 1, 47.2 +/- 12.9 pg/ml; day 2, 21.0 +/- 6.7 pg/ml; day 3, 15.5 +/- 5.9 pg/ml vs. 8.9 +/- 7.5 pg/ml, p < 0.01). Increased IL-10 concentrations were independently associated with age < 4 years and mortality (p = 0.004 and 0.04, respectively, multivariate linear model). This study demonstrates that IL-6 is increased after TBI in children to levels similar to those reported in adults and is the first to show that IL-10 is increased in CSF of humans after TBI. These data suggest that there may be an age-dependent production of IL-10 after TBI in children.