Modification of Acute Experimental Autoimmune Encephalomyelitis in the Lewis Rat by Oral Administration of Type 1 Interferons

Abstract

The effect of orally administered type 1 interferons on the severity of acute experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease, was examined by inoculation of Lewis rats with guinea pig myelin basic protein (GPMBP) and complete Freund's adjuvant. Rats were fed either rat species-specific or human recombinant type 1 interferon (IFN) or mock IFN daily for 7 days preceding immunization and for 21 days thereafter. There was a significant decrease in the clinical score and inflammatory foci in animals fed 5000 units IFN compared with mock-treated animals. There was a significant decrease in clinical score and number of inflammatory foci in spinal cord in animals fed orally 5000 units human recombinant IFN-α PO compared with SC 5000 units recombinant human IFN-α. Oral administration of type 1 interferon, as opposed to subcutaneous administration, inhibited the secretion of IFN-γ from ConA-activated draining popliteal lymph node cells compared with mock-fed animals. These experiments demonstrate that acute EAE is more effectively inhibited by equivalent amounts of orally in contrast to parenterally administered IFN-α. These results suggest that type 1 IFNs are active by the oral route and have significant clinical and histologic effects in acute autoimmune disease.