title: Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro.
abstract: 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.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009457:Neuroglia / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D011994:Recombinant Proteins; D013116:Spinal Cord / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma