Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro

Ann Neurol. 1988 Apr;23(4):339-46. doi: 10.1002/ana.410230405.


Recombinant human tumor necrosis factor (rhTNF) has been tested for its effect on myelinated cultures of mouse spinal cord tissue. As controls, recombinant human interferon gamma (rhIFN) and interleukin-2 (rhIL-2) were tested, as well as T-cell supernatants, antigalactocerebroside serum, and normal culture medium. It was found that rhTNF induced delayed-onset (18-24 hr) oligodendrocyte necrosis and a type of myelin dilatation peculiar to this system. Some nerve fibers progressed to demyelination by 72 hours. The myelin dilatation was not reversible by return to normal feeding solution for 3 days. In contrast, rhIFN, rhIL-2, T-cell supernatants, and normal medium had little or no effect on cultures. This mechanism differs from other immune-mediated mechanisms in that it appears that a physiological (not structural) demyelination occurs initially without overt destruction of the myelin sheath. These observations are relevant to the evolution of the multiple sclerosis plaque: dysfunction of ionic channels might contribute to the eventual demise of oligodendrocytes and axons in the longstanding lesion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Mice
  • Myelin Sheath / drug effects*
  • Myelin Sheath / pathology
  • Myelin Sheath / ultrastructure
  • Neuroglia / drug effects*
  • Oligodendroglia / drug effects*
  • Oligodendroglia / pathology
  • Oligodendroglia / ultrastructure
  • Recombinant Proteins
  • Spinal Cord / cytology*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Interleukin-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma