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Toxicity in neuronal cells caused by cerebrospinal fluid from pneumococcal and gram-negative meningitis
M G Täuber1, M Sachdeva, S L Kennedy
1Microbial Pathogenesis Unit, San Francisco General Hospital, CA.
Abstract:
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.
Insights
Tumor necrosis factor (TNF) drives neurotoxicity in early meningitis models. However, in established pneumococcal meningitis, other factors contribute to neuronal cell damage beyond TNF.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Meningitis, an inflammation of the membranes surrounding the brain and spinal cord, can lead to severe neurological damage.
- Identifying the specific neurotoxic factors involved in different types of meningitis is crucial for developing targeted treatments.
Purpose of the Study:
- To investigate the role of tumor necrosis factor (TNF) and other potential neurotoxic factors in cerebrospinal fluid (CSF) from rabbits with experimentally induced meningitis.
- To differentiate the neurotoxic mechanisms in early-stage meningitis versus established pneumococcal meningitis.
Main Methods:
- Neuronal cell line (HN33.1) exposure to CSF from rabbits with pneumococcal or Escherichia coli meningitis.
- Assessment of cytotoxicity using a soluble TNF receptor to block TNF-mediated effects.
- Evaluation of CSF toxicity at 2 hours and 6 hours post-induction of meningitis.
Main Results:
- CSF from all meningitis models induced significant cytotoxicity.
- In early stages (2h) of E. coli, endotoxin, or pneumococcal cell wall meningitis, toxicity was primarily mediated by TNF.
- In established pneumococcal meningitis (6h), CSF retained significant cytotoxicity even in the presence of a TNF receptor blocker, indicating the involvement of non-TNF factors.
Conclusions:
- Tumor necrosis factor (TNF) is a key neurotoxin in early meningitis, particularly E. coli and endotoxin-induced.
- Established pneumococcal meningitis involves additional neurotoxic components beyond TNF, contributing to neuronal cell damage.
- Further research is needed to identify these non-TNF neurotoxic factors in pneumococcal meningitis.