Abstract

Over the past decade, much has changed on the landscape of meningitis. The purpose of this study was to investigate the involvement of nitric oxide (NO) and tumor necrosis factor alpha (TNF-a) in the pathogenesis of childhood meningitis. We measured the concentration of NO^-₂ (a stable metabolite of NO) and TNF- a in serial samples of cerebrospinal fluid (CSF) from 21 children with septic and 18 with aseptic meningitis and 20 control patients without meningitis. Significantly higher CSF NO^-₂ concentrations were detected in those with bacterial meningitis than those with aseptic meningitis (27.6 +/- 26.8 versus 12.2 +/- 12.3 µmol/l; P<0.001) or among non-meningitis subjects (13.2 +/- 24.2 µmol/l; P<0.0001). Clinical and laboratory improvement following administration of antibiotics and dexamethasone was associated with a fall in CSF (NO^-₂) to normal levels in these patients. The mean (+/- SD) of TNF-a concentration in septic meningitis was 148.74 +/- 338.77 pg/ml. There was significantly more TNF-alpha than aseptic meningitis (6.85 +/- 17.93 pg/ml; P<0.001) or non-meningitis (7.67 +/- 16.07 pg/ml; P<0.001). We did not find a correlation between CSF nitrate/nitrite levels and TNF-a (r = 0.046). Our findings indicate that NO and TNF-a production are enhanced in the CSF compartment of children with septic meningitis and support the hypothesis that both markers are involved in the pathophysiology of septic meningitis.