-Original-

Tumor Necrosis Factor-α-induced Mononuclear Cell Death May Contribute to Polymorphonuclear Cell Predominance in the Cerebrospinal Fluid of Patients with Bacterial Meningitis

Yasuhiko Kawakami^1,2, Mitsutoshi Tsukimoto³, Kentaro Kuwabara^1,4, Takehisa Fujita^1,5, Osamu Fujino^1,6, Shuji Kojima³ and Yoshitaka Fukunaga^1,4

¹Department of Pediatrics, Graduate School of Medicine, Nippon Medical School
²Department of Pediatrics, Nippon Medical School Tama Nagayama Hospital
³Department of Radiation Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science
⁴Department of Pediatrics, Nippon Medical School Hospital
⁵Department of Pediatrics, Nippon Medical School Musashi Kosugi Hospital
⁶Department of Pediatrics, Nippon Medical School Chiba Hokusoh Hospital

Background: Bacterial meningitis is characterized by a marked predominance of polymorphonuclear leukocytes (PMNs: segmented granulocytes or neutrophils) in the cerebrospinal fluid (CSF), whereas aseptic meningitis is characterized by a predominance of mononuclear leukocytes (MNs: lymphocytes or monocytes). However, the pathophysiology of this predominance of PMNs in the CSF of patients with bacterial meningitis has never, to our knowledge, been clearly described.
Methods: To investigate the predominant cell components of CSF from pediatric patients with bacterial meningitis, we investigated cell death in association with levels of tumor necrosis factor-alpha (TNF-α) in the CSF, using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and flow cytometry.
Results: The MTT assay of the CSF revealed that the PMNs had survived, while the MNs rapidly had undergone cell death. Although PMNs survived in CSF with high levels of TNF-α, PMN apoptosis was demonstrated with flow cytometry.
Conclusions: The present study suggests that the pathophysiology of PMN predominance in the CSF of patients in the acute phase of bacterial meningitis is related to the rapid cell death of MNs and the survival of PMNs brought about by high levels of TNF-α.

J Nippon Med Sch 2011; 78: 360-366

Keywords
bacterial meningitis, polymorphonuclear leukocytes, mononuclear leukocytes, cerebrospinal fluid, tumor necrosis factor-alpha

Correspondence to
Yasuhiko Kawakami, MD, Department of Pediatrics, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo 206-8512, Japan
kawakami@nms.ac.jp

Received, April 5, 2011
Accepted, June 28, 2011