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

Tang, Daolin MD, PhD; Kang, Rui MD, PhD; Cao, Lizhi MD; Zhang, Guoyuan MD; Yu, Yan MD; Xiao, Weimin MD, PhD; Wang, Haichao PhD; Xiao, Xianzhong MD, PhD

doi: 10.1097/01.CCM.0000295316.86942.CE
Pediatric Critical Care

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.

From the Department of Pathophysiology, Xiangya School of Medicine (DT, WX, XX), and the Department of Pediatrics, Xiangya Hospital (RK, LC, GZ, YY), Central South University, Changsha, Hunan, P. R. China; the College of Optometry, University of Houston, Houston, TX (WX); and the Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY (HW).

Dr. Tang and Dr. Kang contributed equally to this article.

Supported, in part, by grants 30500485, 30330280, and 30371382 from the National Natural Sciences Foundation of China; grant G2000056908 from the Major National Basic Research Program of China; grant 2005-75239 from the Innovative Program of Central South University for Post-graduate Research; and grants NIGMS, GM063075, and GM070817 from the National Institute of General Medical Sciences (HW).

The authors have not disclosed any potential conflicts of interest.

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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins