Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.