Bioactive and inactive forms of tumor necrosis factor-alpha 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-alpha (TNF alpha) levels were determined by ELISA. TNF alpha immunoreactivity was found in spinal fluid of 10 meningitis patients and one nonmeningitis patient, whereas 7 sera, 5 from meningitis patients, contained TNF alpha. Levels were significantly higher in spinal fluids than in serum samples, and the TNF alpha bioactivity of spinal fluids and sera was considerably below predictions based on ELISA measurements. Gel filtration chromatography demonstrated the presence of both polymeric (greater than 200 kDa) and oligomeric (10-40 kDa) TNF alpha 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 TNF alpha 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 TNF alpha in meningitis.