Toxicity in Neuronal Cells Caused by Cerebrospinal Fluid from Pneumococcal and Gram-Negative Meningitis

• Published in: The Journal of infectious diseases Vol. 166; no. 5; pp. 1045 - 1050
• Main Authors: Täuber, Martin G., Sachdeva, Meena, Kennedy, Stephen L., Loetscher, Hansruedi, Lesslauer, Werner
• Format: Journal Article
• Language: English
• Published: United States University of Chicago Press 01-11-1992
• Subjects: Animals; Bacterial meningitis; Cell Death; Cell Line; Cell lines; Cell walls; Cerebrospinal fluid; Cerebrospinal Fluid - physiology; Cytotoxicity; Endotoxins; Escherichia coli; Escherichia coli meningitis; L-Lactate Dehydrogenase - metabolism; Major Articles; Meningitis, Bacterial - cerebrospinal fluid; Meningitis, Pneumococcal - cerebrospinal fluid; Neurons; Neurons - drug effects; Neurons - pathology; Pneumococcal meningitis; Rabbits; Recombinant Proteins - pharmacology; Streptococcus pneumoniae; Toxicity; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/166.5.1045

To identify neurotoxic factors in meningitis, a neuronal cell line (HN33.1) was exposed to cerebrospinal fluid (CSF) obtained from rabbits with pneumococcal meningitis or Escherichia coli meningitis or 2 h and 6 h after meningitis was induced by proinflammatory bacterial products (pneumococcal cell walls, endotoxin). CSF from all types of meningitis induced similar degrees of cytotoxicity. When a soluble tumor necrosis factor (TNF) receptor that completely blocked TNF-mediated toxicity at$10^{-7}$M was used, all toxicity in meningitis caused by E. coli, endotoxin, or pneumococcal cell wall administration (2 h afterwards) was mediated by TNF. In contrast, CSF from animals with meningitis caused by live pneumococci or pneumococcal cell wall injection (6 h afterwards) retained cytotoxicity in the presence of the TNF receptor. Thus, in established pneumococcal meningitis, but not in the other forms of meningitis, TNF is not the only component toxic in this neuronal cell line.