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PEDIATRICS Vol. 112 No. 5 November 2003, pp. 1103-1107

Cytokine and Cellular Inflammatory Sequence in Enteroviral Meningitis

Masatoki Sato, MD*, Mitsuaki Hosoya, MD*, Ken Honzumi, PhD*, Mikako Watanabe, MD§, Norio Ninomiya, MD§, Shiro Shigeta, MD{ddagger} and Hitoshi Suzuki, MD*

* Departments of Pediatrics
{ddagger} Microbiology, Fukushima Medical University, School of Medicine, Fukushima, Japan
§ Jyusendo General Hospital, Koriyama, Japan

Objective. To clarify the sequence of cytokines and inflammatory cells in enteroviral meningitis.

Methods. Cerebrospinal fluid (CSF) was collected from 86 patients who received a diagnosis of enteroviral meningitis after detection of the enteroviral genome in the CSF using polymerase chain reaction. Twenty-one of 86 patients had repeated lumbar punctures. Cytokine concentrations were measured acutely and in 32 samples collected during recovery.

Results. The proinflammatory cytokines (interleukin [IL]-6, IL-8, and interferon-{gamma}) were detected at significantly higher concentrations during the acute phase when enteroviral genomes were present. Proinflammatory cytokines decreased to normal levels in the recovery phase when enteroviral genomes disappeared. Anti-inflammatory concentrations (IL-10 and transforming growth factor-ß1) were significantly higher in the recovery phase than in the acute phase. Of the 86 CSF samples collected in the acute phase, 11 had no pleocytosis (<10 white blood cells/mm3). In 7 of those 11 CSF samples, IL-6 and IL-8 levels were as high as those in the 75 samples with pleocytosis (≥10 white blood cells/mm3). Seven patients were considered to be in the initial stage of their illness when production of proinflammatory cytokines were high but leukocytes had not yet infiltrated the cerebrospinal cavity.

Conclusions. The inflammatory process observed in human enteroviral meningitis is comparable with that observed in animal models: 1) infection induces proinflammatory cytokine production, followed by infiltration of white blood cells into the infected area, and 2) inflammation is terminated by the anti-inflammatory cytokines that are produced when pathogens are eliminated.

Key Words: viral meningitis • enterovirus • cytokine • inflammatory cells

Abbreviations: WBC, white blood cell • IL, interleukin • TNF, tumor necrosis factor • IFN, interferon • TGF, transforming growth factor • CSF, cerebrospinal fluid • PCR, polymerase chain reaction • ELISA, enzyme-linked immunosorbent assay

Received for publication Jan 25, 2002; Accepted Apr 17, 2003.


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