A pilot study to detect high mobility group box 1 and heat shock protein 72 in cerebrospinal fluid of pediatric patients with meningitis

Objective: To determine whether cerebrospinal fluid (CSF) levels of high mobility group box 1 (HMGB1) or heat shock protein 72 (Hsp72) are elevated in patients with meningitis. Design: Prospective study of four cohorts of patients. Setting. Intensive care unit and infectious disease clinic of pediatrics at the Xiangya Hospital. Patients. A total of 104 children (13 with bacterial meningitis, 38 with aseptic meningitis, 7 with tuberculous meningitis, and 46 without meningitis). Interventions: None. Measurements and Main Results: At the time of admission, CSF samples were obtained from 104 patients with suspected meningitis and examined for the presence of invading pathogens, changes in CSF white blood cell counts, and protein and/or glucose concentrations. Based on CSF parameters, 13, 38, and 7 patients were diagnosed as having bacterial, aseptic, and tuberculous meningitis, respectively. All CSF samples were assayed for HMGB1 or Hsp72 using semiquantitative Western blot analysis. CSF levels of HMGB1 were elevated in patients with bacterial meningitis or aseptic meningitis but were four times higher in patients with bacterial meningitis vs. aseptic meningitis. There was a significant correlation between CSF HMGB1 levels and CSF white blood cell counts and glucose levels in patients with bacterial meningitis. Similarly, CSF levels of Hsp72 were significantly elevated in patients with bacterial meningitis or tuberculous meningitis and correlated well with CSF white blood cell counts in patients with bacterial meningitis or tuberculous meningitis. Conclusions. CSF levels of HMGB1 and Hsp72 were significantly higher in patients with bacterial meningitis than those with aseptic meningitis and correlated well with CSF white blood cell counts in patients with bacterial (but not aseptic) meningitis.