Modification of the clinical and histopathologic expression of experimental allergic encephalomyelitis by the vasoactive amine antagonist cyproheptadine

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune syndrome that can be induced in Lewis rats by myelin basic protein (BP) in complete Freund's adjuvant (CFA). Rats that have recovered from a primary episode of EAE display paradoxical long-term resistance to EAE reinduction by BP-CFA. Previous observations indicated, however, that clinical disease could be reinduced in convalescent rats by a concomitant secondary challenge with BP-CFA + Bordetella pertussis extract (PERT). Vascular permeability changes in the central nervous system (CNS) paralleled disease reinduction. To further probe the relationship between disease reinduction and vascular permeability, convalescent rats were treated with the vasoactive amine antagonist cyproheptadine (CYP) prior to a secondary challenge with BP-CFA + PERT. Data presented here indicate that CYP treatment results in substantial protection of convalescent rats from clinical disease reinduction by BP-CFA + PERT. CYP did not, however, prevent the development of new CNS lesions. CYP therapy also altered the clinical course of EAE induced by a primary injection of BP-CFA + PERT. In these rats, there was a delay in the onset of clinical signs as well as in the appearance of CNS lesions. Nevertheless, both CYP-treated and untreated naive rats challenged with BP-CFA + PERT eventually developed severe and usually lethal EAE. The effect of CYP on EAE induced in naive rats without including PERT in the sensitization protocol was also evaluated. In contrast to the mitigating effect of CYP on EAE induced or reinduced by BP-CFA + PERT, CYP treatment did not affect the clinical course or the development of CNS lesions in rats challenged with BP-CFA alone. Likewise, the passive transfer of EAE, mediated by mitogen-stimulated cells obtained from BP-CFA-sensitized donors, was not affected by CYP treatment. Collectively, these data indicate that CYP therapy altered the expression of EAE induced by regimens that included PERT, but did not affect EAE induced without PERT. In view of the opposing effects of PERT and CYP on vascular permeability, these data are consistent with the hypothesis that alterations in vascular permeability may play a crucial role in controlling the expression of autoimmune neurological diseases.