Immunological and cytological studies of autoimmune demyelination and multiple sclerosis

The early history of experimental allergic encephalomyelitis is reviewed from the point of view of the characterization and recognition of myelin basic protein and the active agent in acid-fast bacilli, namely muramyl dipeptide. Protocols effective in inducing demyelination are pinpointed. Special attention is paid to the protocol which depends on pretreating guinea pigs with muramyl dipeptide and foreign protein followed by a second injection of foreign protein and then the animals are injected with myelin basic protein and Freund's complete adjuvant. Variations in the timing and amounts of muramyl dipeptide are described as are their effects on the demyelination. The myelin breakdown has been studied with a monoclonal antibody reactive to P2. Similar pretreatment enhances the demyelination in Semliki Forest virus infection in mice. The changes in the blood brain barrier are found at 7 days after the myelin basic protein is injected and show grossly increased uptake by the cerebral vascular endothelium of IgG and perivascular uptake of IgG. The changes in the cerebrospinal fluid (CSF) proteins are described (IgG and albumin). Studies of P2 protein in the CSF by means of a new ELISA technique have been performed on human CSF in multiple sclerosis.