High-Mobility Group Box 1 Protein in CSF of Patients with Subarachnoid Hemorrhage
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High-mobility group box 1 protein (HMGB1) is a nuclear factor that is a potent proinflammatory mediator, and may trigger increases in other inflammatory cytokines. The inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH) have been reported previously, but HMGB1 has not. In this study, we measured HMGB1 and the inflammatory cytokines in the CSF of patients with SAH.
CSF samples were collected on days 3, 7, and 14 from the drainage tubes of the postaneurysm clips of 39 patients with SAH. HMGB1, interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α) were measured in the CSF, and compared between the patients with favorable (good recovery and moderate disability) and unfavorable outcomes (severe disability, vegetative state, and death) at 3 months.
In the unfavorable outcome group, HMGB1 (P = 0.017), IL-6 (P = 0.003), IL-8 (P = 0.041), and TNF-α (P = 0.002) were significantly increased. HMGB1 correlated significantly with IL-6, IL-8, and TNF-α (R = 0.672, 0.421, and 0.697, respectively).
HMGB1 was increased in the CSF of SAH patients with an unfavorable outcome, as were the other cytokines. These results suggest that HMGB1 and cytokines are related to the brain damage observed after SAH. HMGB1 might play a key role in the inflammatory response in the CNS of SAH patients.
KeywordsHMGB1 Cytokines Subarachnoid hemorrhage Glasgow outcome scale Neuroinflammation
This clinical study was supported by a research project grant from the Japanese Ministry of Health, Labor, and Welfare (No. H18-trans-general-003). We are grateful to Kiyoshi Ichihara and Yuji Koyanagi (Department of Laboratory Science, Yamaguchi University Graduate School of Medicine) for their valuable statistical assistance, Taku Miyasho (Rakuno Gakuen University) and Hitomi Ikemoto (Yamaguchi University) for their valuable technical assistance with the measurements. We also thank Masako Ueda for assistance with the grant-related paperwork.
Conflict of interest statement
All work was conducted independently of the funding parties, except for a governmental grant. This grant had no influence on the decisions relating to the study design or publication.
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