Inhibition of Theiler's Virus-induced demylination in vivo by tumor necrosis factor alpha

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Abstract
Employing a murine model of multiple sclerosis which utilizes intracraniai injection of Theiier's virus murine encephalomyelitis (TMEV) Into SJL/J mice, we tested the potential role of tumor necrosis factor alpha (TNF-a) In ameliorating CNS demyeiination. Infection with TMEV caused early grey matter Inflammation (7 days post-Infection) in the brain and spinal cord followed by chronic demyeiination (35 days post-infection) in the spinal cord. Administration of recombinant human or mouse TNF-a starting 12 h prior to infection and then three times weekly had minimal effect on development of grey matter Inflammation in the spinal cord. In contrast, TNF-a dramatically reduced demyeiination present In spinal cord on days 14 and 35 after TMEV infection (P < 0.01) when compared to controls. CNS virus tlters of TMEV were not modified by TNF-a administration as measured on days 7, 14, and 35 following infection. In vivo administration of TNF-a inhibits TMEV-induced demyeiination in susceptible SJL/J mice without affecting virus replication In the CNS.