Short-term treatment with interferon-α/β promotes remyelination, whereas long-term treatment aggravates demyelination in a murine model of multiple sclerosis
✍ Scribed by M. Kariuki Njenga; Michael J. Coenen; Nannette DeCuir; Hung-Yueh Yeh; Moses Rodriguez
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 346 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
The mechanisms by which type I interferons (IFN) reduce the rate and severity of exacerbations in multiple sclerosis are unknown. We utilized a model of multiple sclerosis to determine the extent of demyelination and remyelination in Theiler's murine encephalomyelitis virus (TMEV)infected SJL/J mice treated with mouse IFN-␣/ for a short (5 weeks) or a long (16 weeks) period. All mice were chronically infected with TMEV to simulate the clinical situation in multiple sclerosis. Short-term IFN-␣/ treatment increased the percent of remyelinated spinal cord white matter by threefold when compared with phosphate-buffered saline (PBS) treatment (P Ͻ 0.02), but it did not affect the extent of demyelination. In contrast, long-term IFN-␣/ treatment increased the extent of demyelination by twofold (P Ͻ 0.03). Long-term treatment increased the absolute area of remyelination, but the percent remyelination as a function of area of demyelination was not changed because of increased demyelination. An immunomodulatory mechanism may have contributed to the effect of IFN-␣/ on white matter pathology because treated mice had higher anti-TMEV IgGs in serum and demonstrated decreased numbers of B and T lymphocytes infiltrating the central nervous system (CNS). There was no correlation between the level of anti-IFN-␣/ antibodies and the extent of demyelination or remyelination. These results indicate that the length of type I IFN treatment may have paradoxical effects on demyelination and remyelination.