Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study
Abstract 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...
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BMC
2025-01-01
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| Online Access: | https://doi.org/10.1186/s12879-025-10476-7 |
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| author | Takeshi Matsushige Hirofumi Inoue Madoka Hoshide Fumitaka Kohno Hikaru Kobayashi Kiyoshi Ichihara Takashi Ichiyama Shunji Hasegawa |
| author_facet | Takeshi Matsushige Hirofumi Inoue Madoka Hoshide Fumitaka Kohno Hikaru Kobayashi Kiyoshi Ichihara Takashi Ichiyama Shunji Hasegawa |
| author_sort | Takeshi Matsushige |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-1b846f4336e44bb48aa2c2d2eeb22043 |
| institution | Kabale University |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj-art-1b846f4336e44bb48aa2c2d2eeb220432025-01-26T12:17:17ZengBMCBMC Infectious Diseases1471-23342025-01-0125111010.1186/s12879-025-10476-7Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort studyTakeshi Matsushige0Hirofumi Inoue1Madoka Hoshide2Fumitaka Kohno3Hikaru Kobayashi4Kiyoshi Ichihara5Takashi Ichiyama6Shunji Hasegawa7Department of Pediatrics, Yamaguchi University Graduate School of MedicineDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineDepartment of Clinical Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of MedicineDivision of Pediatrics, Tsudumigaura Medical Center for Children With DisabilitiesDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineAbstract 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.https://doi.org/10.1186/s12879-025-10476-7Bacterial meningitisCerebrospinal fluidHigh mobility group box 1CytokinePrognosis |
| spellingShingle | Takeshi Matsushige Hirofumi Inoue Madoka Hoshide Fumitaka Kohno Hikaru Kobayashi Kiyoshi Ichihara Takashi Ichiyama Shunji Hasegawa Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study BMC Infectious Diseases Bacterial meningitis Cerebrospinal fluid High mobility group box 1 Cytokine Prognosis |
| title | Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study |
| title_full | Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study |
| title_fullStr | Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study |
| title_full_unstemmed | Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study |
| title_short | Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study |
| title_sort | serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis a retrospective cohort study |
| topic | Bacterial meningitis Cerebrospinal fluid High mobility group box 1 Cytokine Prognosis |
| url | https://doi.org/10.1186/s12879-025-10476-7 |
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