Correlation of interleukin-1β and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Because interleukin-1β (IL-1β) and cachectin (tumor necrosis factor) are though to mediate the body's response to microbial invasion, we measured IL-1β and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF₁; 18 to 30 hours later, CSF₂) from 106 infants and children with bacterial meningitis. In CSF₁, IL-1β was detected in 95% of samples; the mean (±1 SD) concentration was 944±1293 pg/ml. Patients with CSF₁ IL-1β concentrations >500 pg/ml were more likely to have neurologic sequelae (p=0.001). Tumor necrosis factor was present in 75% of CSF₁ samples; the mean concentration was 787±3358 pg/ml. In CSF₂ the mean IL-1β concentration was 135±343 pg/ml, and IL-1β concentrations correlated significantly with CSF₂ leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF₂ specimens of 53 of 106 patients, with a mean concentration of 21±65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1β and higher glucose and lower lactate concentrations in CSF₂, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p≤0.002). Our data suggest a possible role of IL-1β and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.