Matsushige Takeshi, Inoue Hirofumi, Hoshide Madoka, Kohno Fumitaka, Kobayashi Hikaru, Ichihara Kiyoshi, Ichiyama Takashi, Hasegawa Shunji
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
BMC Infect Dis. 2025 Jan 23;25(1):107. doi: 10.1186/s12879-025-10476-7.
Bacterial meningitis (BM) is a life-threatening central nervous system infection with potential for severe neurological sequelae. High mobility group box 1 (HMGB1) is known as a late inflammatory mediator associated with lethal pathology. This study aims to investigate the serial cerebrospinal fluid (CSF) concentrations of HMGB1 in children with BM and its relationship to neurological prognosis.
This retrospective cohort study included children with BM, aseptic meningitis (AM), and controls. CSF samples were collected serially from patients with BM and once from those with AM and controls. HMGB1 and interleukin-6 (IL-6) concentrations were measured using ELISA and bead-based multiplex assays, respectively. Statistical analyses included Mann-Whitney U tests, Kruskal-Wallis tests, and three-way ANOVA to evaluate differences among groups and over time.
HMGB1 levels in the CSF of children with BM were significantly higher than in those with AM and controls (p < 0.001). Inflammatory cytokine IL-6 levels decreased after treatment; however, HMGB1 levels remained elevated in half of the BM patients. Notably, a patient with neurological sequelae exhibited a delayed elevation of HMGB1 until the latest time points. Three-way ANOVA revealed significant differences in the time course of IL-6 and HMGB1 among individuals (p = 0.018).
Elevated CSF HMGB1 levels persist in some children with BM even after treatment, particularly in those with poor neurological outcomes. These findings suggest that delayed elevation of HMGB1 may contribute to severe inflammation and poor prognosis in BM. Further research into HMGB1 as a potential therapeutic target in BM is warranted.
细菌性脑膜炎(BM)是一种危及生命的中枢神经系统感染,有可能导致严重的神经后遗症。高迁移率族蛋白B1(HMGB1)是一种与致命病理相关的晚期炎症介质。本研究旨在调查BM患儿脑脊液(CSF)中HMGB1的系列浓度及其与神经预后的关系。
这项回顾性队列研究纳入了患有BM、无菌性脑膜炎(AM)的儿童以及对照组。对BM患儿的脑脊液样本进行系列采集,对AM患儿和对照组则仅采集一次样本。分别使用酶联免疫吸附测定(ELISA)和基于微珠的多重分析方法测量HMGB1和白细胞介素-6(IL-6)的浓度。统计分析包括曼-惠特尼U检验、克鲁斯卡尔-沃利斯检验和三因素方差分析,以评估组间差异和随时间的变化。
BM患儿脑脊液中的HMGB1水平显著高于AM患儿和对照组(p < 0.001)。治疗后炎症细胞因子IL-6水平下降;然而,一半的BM患儿中HMGB1水平仍保持升高。值得注意的是,一名有神经后遗症的患儿HMGB1水平直到最晚时间点才出现延迟升高。三因素方差分析显示个体间IL-6和HMGB1的时间进程存在显著差异(p = 0.018)。
即使在治疗后,一些BM患儿脑脊液中HMGB1水平仍持续升高,尤其是那些神经预后较差的患儿。这些发现表明,HMGB1的延迟升高可能导致BM中的严重炎症和不良预后。有必要进一步研究将HMGB1作为BM潜在治疗靶点。