Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss

Helmut Butzkueven, Ben Emery, Tania Cipriani, Mark P. Marriott, Trevor J. Kilpatrick

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80 Citations (Scopus)


Autoimmune injury to oligodendrocytes evokes an endogenous response in the central nervous system, which initially limits the acute injury to oligodendrocytes and myelin, and subsequently promotes remyelination. The key molecular and cellular events responsible for this beneficial outcome are incompletely understood. In this article, we utilize murine autoimmune encephalomyelitis (EAE) to focus on the effect of endogenously produced leukemia inhibitory factor (LIF) upon mature oligodendrocyte survival after demyelinating injury. We show that the mRNA for LIF is markedly upregulated in the spinal cord in the context of acute inflammatory demyelination. After clinical disease onset, administration of neutralizing anti-LIF antibodies over a four day period significantly worsens disease severity in two different murine EAE models. We also show that administration of neutralizing antibodies results in reduced activation of the cognate LIF receptor components in the spinal cord. Histologically, anti-LIF antibody administration increases the extent of acute demyelination (P < 0.01) and doubles the oligodendrocyte loss already induced by EAE (P < 0.05), without altering the extent of inflammatory infiltration into the spinal cord. Although acute EAE induces a rapid, three-fold increase in the proliferation of NG2 positive oligodendrocyte progenitors (P < 0.001), this response is not diminished by antagonism of endogenous LIF. We conclude that endogenous LIF is induced in response to autoimmune demyelination in the spinal cord and protects mature oligodendrocytes from demyelinating injury and cell death, thereby resulting in attenuation of clinical disease severity.

Original languageEnglish
Pages (from-to)696-703
Number of pages8
Issue number7
Publication statusPublished or Issued - May 2006
Externally publishedYes


  • Autoimmune demyelination
  • Endogenous
  • Leukemia inhibitory factor
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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