The production of macrophage inflammatory protein-1 alpha in the cerebrospinal fluid at the initial stage of meningitis in children

Neutrophils in the cerebrospinal fluid (CSF) increase during the initial stage of meningitis. Some cytokines induce the accumulation of such neutrophils, and we and other investigators have revealed transient increases in the levels of granulocyte-colony stimulating factor (G-csf) and IL-8 in the CSF of patients with meningitis. To explore the coordination of other cytokines with G-csf and IL-8 in the neutrophil accumulation in the CSF, we herein investigated macrophage inflammatory protein-1 alpha (MIP-1 alpha), which can induce the infiltration of neutrophils. The modulation of MIP-1 alpha levels in the CSF in children with bacterial (n = 10) and aseptic (n = 22) meningitis was examined using an ELISA. MIP-1 alpha levels in the CSF were detectable at the stage with symptoms of meningitis: 289.9 +/- 270.7 ng/L in the bacterial meningitis group and 16.1 +/- 12.5 ng/L in the aseptic meningitis group. These levels decreased with the improvement of symptoms. MIP-1 alpha was not detectable (<6 ng/L) in all of the control patients without meningitis (n = 19). The MIP-1 alpha levels in the CSF showed a significant correlation with the CSF neutrophil counts (r = 0.750, p < 0.0001; n = 80) of meningitis, and the values of MIP-1 alpha (log ng/L)/neutrophil counts (log/L) ratio were calculated(1.003 +/- 0.576). The MIP-1 alpha levels in the serum were significantly lower than those in the CSF (p = 0.0464). We found MIP-1 alpha mRNA in the CSF cells by the reverse transcriptase-PCR method, and high levels of MIP-1 alpha protein in the culture media from mononuclear cells in the CSF in vitro. In summary, The MIP-1 alpha level increases in the CSF at the symptomatic stage of meningitis in children, and its cellular source is, in part, mononuclear cells which have infiltrated the CSF. We propose that MIP-1 alpha, in addition to G-csf and IL-8, plays an important role in the accumulation of neutrophils in the CSF of patients with meningitis.