Bioactive and Inactive Forms of Tumor Necrosis Factor-α in Spinal Fluid from Patients with Meningitis

Twenty-four patients, including 12 with meningitis, were admitted with meningeal symptoms and fever. Their serum and spinal fluid tumor necrosis factor-α (TNFα) levels were determined by ELISA. TNFα immunoreactivity was found in spinal fluid of 10 meningitis patients and one nonmeningitis patient, whereas 7 sera, 5 from meningitis patients, contained TNFα. Levels were significantly higher in spinal fluids than in serum samples, and the TNFα bioactivity of spinal fluids and sera was considerably below predictions based on ELISA measurements. Gel filtration chromatography demonstrated the presence of both polymeric (>200 kDa) and oligomeric (10–40 kDa) TNFα in spinal fluid. Significant bioactivity was obtained only from samples containing oligomeric cytokine. In agreement with previous in vitro findings, these results strongly indicate that bioactive TNFα oligomers form inactive polymers and monomers, which could contribute to the observed in vivo discrepancies between immunoreactive and bioactive protein. Finally, the data support the concept of local central nervous system production of TNFα in meningitis.