Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, China.
Eur J Pediatr. 2024 Aug;183(8):3359-3368. doi: 10.1007/s00431-024-05604-5. Epub 2024 May 15.
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.
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.
This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022.
• Inflammation is an important secondary physiological response to TBI.
• 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.
本研究旨在探讨中度至重度创伤性脑损伤(m-sTBI)患儿早期血浆炎症细胞因子表达谱与临床结局的相关性。
前瞻性纳入 2022 年 11 月至 2023 年 5 月因 m-sTBI 入住我院重症监护病房(ICU)的患儿。入院和入院后第 5-7 天通过流式细胞术检测血浆白细胞介素(IL)-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-17A、干扰素(IFN)-α、IFN-γ和肿瘤坏死因子(TNF)-α浓度。主要结局为院内死亡率。次要结局为 6 个月时采用格拉斯哥结局量表扩展儿科版(GOS-E Peds)评估的功能结局,分为有利(1-4 分)或不利(5-8 分)。
共纳入 50 例患儿和 20 例健康对照者。与健康对照组相比,TBI 患儿的基线 IL-6、IL-8 和 IL-10 水平显著升高。12 例患儿在院死亡。与幸存者相比,非幸存者的基线 IL-6 和 IL-8 水平显著升高。与预后良好的患儿相比,预后不良的患儿的基线 IL-5、IL-6 和 IL-8 水平也显著升高。IL-6 和 IL-8 水平以及运动性格拉斯哥昏迷量表(GCS)评分预测院内死亡率的受试者工作特征曲线(AUC)分别为 0.706、0.754 和 0.776。基线 IL-1β、IL-2、IL-4、IL-10、IL-12p70、IL-17A、IFN-γ、IFN-α和 TNF-α水平与院内死亡率或 6 个月不良结局无关。与幸存者相比,非幸存者在第 5-7 天的 IL-6 和 IL-8 水平与各自的基线相比显著升高。
m-sTBI 后,儿童的血浆炎症细胞因子谱发生明显改变。不同结局 m-sTBI 患儿的 IL-6 和 IL-8 表达趋势不同。血浆 IL-6 和 IL-8 水平升高与院内死亡率和 6 个月不良结局相关。
ChiCTR2200065505,于 2022 年 11 月 7 日在国家临床试验注册中心登记。