Critical threshold for dose of myelin basic protein in murine autoimmune encephalomyelitis

Abstract

The clinical and pathologic features of experimental allergic encephalomyelitis (EAE) in the SJL mouse are described after inoculation with different amounts of myelin basic protein (MBP) in adjuvant. A dose threshold was apparent in that 400 μg produced the most severe central nervous system (CNS) changes. These comprised an extensive multifocal destructive myelitis with minimal demyelination. Doses greater than 400 μg produced less white matter pathology and showed demyelinative rather than destructive lesions. No CNS parenchymal changes were seen in animals given less than 400 μg. Inflammation was invariably present in all animals showing CNS pathology, a prominent cellular component of which was the polymorphonuclear leukocyte. These findings illustrate the relationship of clinical signs and pathologic changes to the dose of MBP administered. Thus, it has been shown that the dose requirements for MBP-induced EAE in the SJL mouse are different from and greater than those for other species and that, unlike rats and guinea pigs, lesions were more extensive. Although demyelination was present, lesions tended to be destructive in type. This murine MBP model may serve as an experimental analog for the acute destructive myelopathies occasionally associated with the human autoimmune demyelinating disorders.