The level of tumor necrosis factor-α producing cells in the spinal cord correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease

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Abstract
The levels of tumor necrosis factor (TNF)-α producing cells were analyzed in mice with Theller's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Using an ELISPOT assay, we demonstrate an increase in TNF-α producing cells in the spinal cords of TMEV-infected SJL/J mice, especially at an active disease stage. The numbers of TNF-α producing cells were extremely high in susceptible SJL/J mice compared with the numbers in resistant BALB/c and C57BL/6 mice. TNF-α producing cells were also immunohistochemically identified in active lesions of TMEV-IDD at acute as well as chronic stages. The percentage of TNF-α producing cells compared with the total number of cells isolated from spinal cords was higher in TMEV-infected SJL/J mice than resistant BALB/c and C57BL/6 mice. Correspondingly, the level of TNF-α was much higher in the culture supernatants of both infiltrating cells in the spinal cords and spleen cells from clinically affected animals than that from similarly treated resistant mice. Treatment of virus-infected mice with a mAb specific for TNF-α at the beginning of the onset of disease suppressed the development of the demyelinating disease. These findings suggest that TNF-α may play an important role in the pathogenicity of TMEV-IDD.

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