Suppression of murine chronic relapsing experimental autoimmune encephalomyelitis by the oral administration of myelin basic protein

Abstract

Chronic relapsing experimental autoimmune encephalomyelitis (EAE), induced in mice by the injection of myelin basic protein (MBP), is a T cell-mediated autoimmune disease characterized by periods of paralysis and remission. We have shown previously that the oral administration of MBP or MBP peptides renders Lewis rats refractory to EAE. This study was undertaken to examine the conditions necessary to produce oral tolerance in a chronic relapsing model of EAE in B10.PL mice. The optimal tolerizing regimen for the mouse was found to be a single feeding of 20 mg of MBP suspended in PBS. To determine the ability to suppress chronic disease, a range of doses (0.4-100 mg) was administered orally in a single dose before challenge. Larger oral doses (20 or 100 mg) of MBP provided the best protection from EAE, while 0.4 mg exacerbated the clinical course of disease. Secretion of the proinflammatory cytokines, IL-2 and IFN-gamma, were lowest in the group fed 20 mg. A single feeding of MBP before challenge or as late as the first day of clinical signs showed significant protection over the relapsing disease course. Once relapsing EAE was established, multiple oral doses of MBP were required to achieve suppression of clinical signs of disease. These findings suggest that vehicle, dosage, and timing are important considerations in the successful application of oral tolerance strategies for suppression of chronic disease processes.