Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-α in the central nervous system

Véronique Taupin, Toufic Renno, Lyne Bourbonnière, Alan C. Peterson, Moses Rodriguez, Trevor Owens

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-α in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-α also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-α at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-α in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalEuropean Journal of Immunology
Volume27
Issue number4
DOIs
StatePublished - Apr 21 1997

Keywords

  • Demyelination
  • Macrophage
  • Microglia
  • Transgenic
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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