Cytokine and cellular inflammatory sequence in enteroviral meningitis.

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-beta1) 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/mm(3)). In 7 of those 11 CSF samples, IL-6 and IL-8 levels were as high as those in the 75 samples with pleocytosis (>or=10 white blood cells/mm(3)). 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.