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Tumour necrosis factor and anti-tumour necrosis factor approach to inflammatory demyelinating diseases of the central nervous system
  1. Krzysztof W Selmaj
  1. Department of Neurology, Medical Academy of Lodz, 22 Kopcinskiego Street, 90–153 Lodz, Poland
  1. Professor Selmaj (kselmaj{at}

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Multiple sclerosis is a primary demyelinating disease in which an inflammatory cell infiltrate represents a characteristic pathological feature of active lesions within the central nervous system (CNS). As the search for anti-myelin antibodies in multiple sclerosis has thus far been unsuccessful, the possibility is raised that cell mediated immune mechanisms orchestrate the pathogenesis of this disease.1 In cellular immune mechanisms cytokines play a particularly important part. Tumour necrosis factors (TNFs) form a unique family of cytokines that are very pleiotropic in nature.2 TNFs demonstrate immunoregulatory activity but they are also involved in the effector arm of cellular immune responses. TNF increases antigen and mitogen induced T lymphocyte activation,3 as well as increasing the generation of cytotoxic T cells.4 Studies both in vitro and in vivo have suggested a role for TNFs in the pathology of multiple sclerosis. In this report, I will summarise data for and against involvement of TNFs in the mechanisms of multiple sclerosis and attempt to apply an anti-TNF approach for future therapeutic strategy for this disease.

Organotypic nerve tissue cultures

An initial interest of TNFα involvement in the pathomechanisms of multiple sclerosis was generated after demonstration that TNFα was capable of inducing delayed onset myelin dilatation and subsequent gradual myelin degradation in organotypic nerve tissue cultures.5 The organotypic nerve tissue cultures have been established from spinal cord tissue explanted from mice embryos. Several cytokines, TNFα, interferon γ, interleukin 1, interleukin 2, interleukin 6 were added to spinal cord cultures at a time when myelination was well advanced. The cultures were examined in living state and after fixation by light and electron microscopy. In the living state, cultures exposed to TNFα showed selective damage to myelin. By light microscopy, myelinated fibres exhibited dilatations of myelin sheath. These swellings were regularly spaced along affected fibres and appeared …

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  • Funding: this work was supported by KBN grant 4P05A 009.14.