PREVENTION OF CHRONIC RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR-I

We have evaluated the effect of the type I (p-55, type beta) soluble t umor necrosis factor receptor (sTNFrI) in an animal model of multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) was induced in SJL/J mice by adoptive transfer of T lymphocytes sensitized to mye lin basic protein (MBP). sTNFrI completely blocked both clinical signs of disease and pathological changes that included CNS demyelination a nd inflammatory cell infiltration. Effective inhibition of disease exp ression was obtained using several different regimens of subcutaneous (s.c.) injection. These included daily doses starring at day 0, every other day injections starting at day 0, daily doses starting an day 4, and two doses separated by 12 h on day 1 and 2. Furthermore, treatmen t with sTNFrI for 15 days completely protected these animals from the recurrent episodes of disease normally associated with adoptively tran sferred EAE. These findings suggest that TNF prays a major causative r ole in EAE and that the sTNFrI may prove to be a useful therapeutic ap proach in multiple sclerosis.