Modification of acute experimental autoimmune encephalomyelitis in the Lewis rat by oral administration of type 1 interferons.
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-alpha PO compared with SC 5000 units recombinant human IFN-alpha. Oral administration of type 1 interferon, as opposed to subcutaneous administration, inhibited the secretion of IFN-gamma 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-alpha. These results suggest that type 1 IFNs are active by the oral route and have significant clinical and histologic effects in acute autoimmune disease.
Brod
S A
SA
Department of Neurology, University of Texas Health Science Center at Houston 77030, USA.
Scott
M
M
Burns
D K
DK
Phillips
J T
JT
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant; D006168:Guinea Pigs; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D004676:Myelin Basic Protein; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D007370:Interferon Type I; D016898:Interferon-alpha; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D003208:Concanavalin A; D016899:Interferon-beta; D007371:Interferon-gamma; D005620:Freund's Adjuvant