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Short‐term treatment with interferon‐α/β promotes remyelination, whereas long‐term treatment aggravates demyelination in a murine model of multiple sclerosis
Author(s) -
Njenga M. Kariuki,
Coenen Michael J.,
DeCuir Nannette,
Yeh HungYueh,
Rodriguez Moses
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000301)59:5<661::aid-jnr9>3.0.co;2-e
Subject(s) - remyelination , multiple sclerosis , medicine , encephalomyelitis , demyelinating disease , immunology , myelin , central nervous system , experimental autoimmune encephalomyelitis , white matter , magnetic resonance imaging , radiology
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‐α/β 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‐α/β treatment increased the percent of remyelinated spinal cord white matter by threefold when compared with phosphate‐buffered saline (PBS) treatment ( P < 0.02), but it did not affect the extent of demyelination. In contrast, long‐term IFN‐α/β treatment increased the extent of demyelination by twofold ( P < 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‐α/β 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‐α/β 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. J. Neurosci. Res. 59:661–670, 2000 © 2000 Wiley‐Liss, Inc.