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Detection of a gliotoxic activity in the cerebrospinal fluid from multiple sclerosis patients
A Ménard1, R Pierig, J Pelletier
1INSERM Laboratoire de Neuromodulations Interactives et Neuropathologies - 17, Paris, France.
Abstract:
We recently showed that peripheral blood cell supernatants from multiple sclerosis (MS) patients, containing reverse transcriptase activity and retroviral RNA from the newly human identified multiple sclerosis retrovirus (MSRV), also secrete a cytotoxin which induces death of primary mouse cortical glial cells. We have hypothesized that macrophages could release this cytotoxin in the cerebrospinal fluid. The cerebrospinal fluid cytotoxicity from 166 patients with various neurological diseases (including MS patients) was tested on glial cells in vitro. Our bioassay shows that a glial cytotoxic activity is significantly present in cerebrospinal fluid from patients with relapsing-remitting MS at relapse. Since this cytotoxic activity seems to correlate with active cases of MS, it may represent a critical pathogenic factor in the neuropathology of MS.
Insights
Cerebrospinal fluid from multiple sclerosis (MS) patients contains a glial cytotoxic activity. This activity, potentially released by macrophages, correlates with active MS relapses and may drive MS neuropathology.
Area of Science:
- Neuroimmunology
- Retroviral research
- Cellular toxicology
Background:
- Peripheral blood cells of multiple sclerosis (MS) patients release a cytotoxin linked to the multiple sclerosis retrovirus (MSRV).
- Macrophages are hypothesized to be the source of this cytotoxin in cerebrospinal fluid (CSF).
Purpose of the Study:
- To investigate the presence and significance of glial cytotoxic activity in the cerebrospinal fluid of patients with neurological diseases, particularly MS.
- To determine if CSF cytotoxicity correlates with active MS relapses.
Main Methods:
- A bioassay was developed to test cerebrospinal fluid (CSF) cytotoxicity on primary mouse cortical glial cells in vitro.
- CSF samples were collected from 166 patients diagnosed with various neurological diseases, including MS.
Main Results:
- A significant glial cytotoxic activity was detected in the CSF of patients experiencing relapsing-remitting MS during relapse.
- This cytotoxic activity was found to be significantly present in active MS cases.
Conclusions:
- The study identifies a glial cytotoxic factor in the CSF of active MS patients.
- This CSF-associated cytotoxicity may play a critical role in the neuropathology of multiple sclerosis.