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Recombinant human IL-6 suppresses demyelination in a viral model of multiple sclerosis
M Rodriguez1, K D Pavelko, C W McKinney
1Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Abstract:
We used a murine model of multiple sclerosis (MS) induced by Theiler's murine encephalomyelitis virus (TMEV) to test the effect of IL-6 on central nervous system (CNS) demyelination. Administration of human rIL-6 (2.5 micrograms/dose), beginning one day before infection and then twice daily for 28 days, dramatically reduced demyelination and inflammation in the spinal cord of susceptible SJL/J mice. Benefit also was observed when rIL-6 was used as a therapeutic agent and begun on day 15 after infection, a time in which there is the first evidence of inflammation and demyelination in the spinal cord. Suppression of myelin damage by treatment with rIL-6 was associated with fewer virus Ag-positive cells in the spinal cord. Infectious CNS virus titers, as measured by plaque assay, were reduced in rIL-6-treated animals on day 15 after infection, but not on day 7, 22, or 29 after infection. Total serum Igs and virus-specific Igs, as detected by indirect ELISA, were increased markedly in rIL-6-treated mice, whereas no effect was observed on TMEV-neutralizing Ab titers. In vivo administration of rIL-6 inhibited a murine CNS-demyelinating disease induced by a virus, suggesting that this IL may have application for the treatment of human MS.
Insights
Interleukin-6 (IL-6) significantly reduced central nervous system (CNS) demyelination and inflammation in a mouse model of multiple sclerosis (MS). This suggests IL-6 may be a potential therapeutic agent for treating human MS.
Area of Science:
- Neuroimmunology
- Virology
- Demyelinating Diseases
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS).
- Theiler's murine encephalomyelitis virus (TMEV) infection in mice serves as a model for studying MS pathogenesis.
- The role of interleukin-6 (IL-6) in TMEV-induced demyelination requires further investigation.
Purpose of the Study:
- To investigate the therapeutic potential of interleukin-6 (IL-6) in a murine model of multiple sclerosis (MS).
- To determine the effect of IL-6 on TMEV-induced central nervous system (CNS) demyelination and inflammation.
Main Methods:
- A murine model of MS was established using Theiler's murine encephalomyelitis virus (TMEV) in SJL/J mice.
- Recombinant human IL-6 (rIL-6) was administered prophylactically and therapeutically.
- Demyelination, inflammation, viral antigen-positive cells, viral titers, and antibody responses were assessed.
Main Results:
- Prophylactic and therapeutic administration of rIL-6 significantly reduced spinal cord demyelination and inflammation.
- rIL-6 treatment led to fewer virus antigen-positive cells and reduced viral titers at day 15 post-infection.
- Serum immunoglobulin levels increased in rIL-6 treated mice, but TMEV-neutralizing antibody titers were unaffected.
Conclusions:
- In vivo administration of IL-6 effectively suppressed viral-induced CNS demyelinating disease in mice.
- IL-6 demonstrates potential as a therapeutic agent for human multiple sclerosis.