Experimental autoimmune encephalomyelitis: antigen-induced inhibition of biochemical and immunohistological...

A comprehensive biochemical, immunological, and histological study was undertaken during suppression of experimental autoimmune encephalomyelitis (EAE) induced by antigen-specific inhibition of the immune response. Pretreatment of Wistar rats by intraperitoneal administration of low doses of saline-soluble bovine myelin or myelin basic protein (MBP) but not with ovalbumin suppresses the appearance of the clinical symptoms of EAE induced by sensitization with bovine myelin in complete Freund's adjuvant. Analysis of the central nervous system (CNS) of animals pretreated with MBP or whole myelin shows inhibition of the diminution of MBP and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity observed in the EAE animals or in rats pretreated with ovalbumin. With respect to the CNS lipid content, these suppressive treatments abolish the increase in esterified cholesterol and partially revert the diminution in the content of cerebrosides and total cholesterol characteristic of the acute stage of the disease. Concomitantly, meningeal and parenchymal infiltration with mononuclear cells and deposits of immunoglobulins in the infiltrated regions as well as in spinal cord motor neurons were reduced. Analysis of the humoral response to myelin antigens shows that all EAE as well as treated animals developed antibodies to MBP and other myelin proteins. However, a higher incidence and level of these antibodies was observed in nontreated EAE animals and MBP- and ovalbumin-treated rats, while rats treated with total bovine myelin showed a highly reduced humoral response. The present results indicate that intraperitoneal treatment with soluble forms of myelin antigens, concomitant with the suppression of the clinical symptoms of the disease, markedly reduces the biochemical and histological alterations occurring in EAE animals and produces changes in the autoimmune humoral response.