Short-term treatment with interferon-α/β promotes remyelination, whereas long-term treatment aggravates demyelination in a murine model of multiple sclerosis

M. Kariuki Njenga, Michael J. Coenen, Nannette DeCuir, Hung Yueh Yeh, Moses Rodriguez

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)661-670
Number of pages10
JournalJournal of Neuroscience Research
Volume59
Issue number5
DOIs
StatePublished - Mar 16 2000

Keywords

  • Antibodies
  • B-lymphocytes
  • Central nervous system
  • T-lymphocytes
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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