A histological dose-response effect in guinea-pigs injected with graded amounts of basic protein and peptides from human brain

Abstract

In experimental autoimmune encephalomyelitis (EAE) in guinea-pigs produced by human encephalitogenic basic protein and peptides derived therefrom, the amount of encephalitogen injected could be related to the incidence and severity of the ensuing EAE, assessed “clinically” and histologically. Injection of encephalitogen as a divided dose into 2 footpads, as opposed to a single dose, considerably increased the severity and incidence of ensuing EAE. There was poor correlation between clinically and histologically diagnosed EAE; certain regions of the basic protein might more readily induce typical histological lesions and other regions clinical disease.

With larger doses of encephalitogenic protein and peptides the predominant histological abnormality was a “vascular” lesion without demyelination, resembling that described in EAE induced with whole nervous tissue. Margination of cerebral and meningeal vessels by polymorphonuclear leucocytes was noted, as the only histological change, occasionally after Freund's adjuvant alone, and in guinea-pigs with mild neurological disease after low doses of protein and peptide encephalitogens.