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Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders

Departmant of Neurology, University of Maryland School of Medicine, Baltimore Maryland, Neurology and Research Services, Baltimore VAMC, Baltimore, Maryland

H Jiang

Departmant of Neurology, University of Maryland School of Medicine, Baltimore Maryland

P S Subramaniam

Department of Microbiology and Cell Science, University of Florida, Gainesville, USA

H M Johnson

Department of Microbiology and Cell Science, University of Florida, Gainesville, USA

S S Dhib-Jalbut

Departmant of Neurology, University of Maryland School of Medicine, Baltimore Maryland, Neurology and Research Services, Baltimore VAMC, Baltimore, Maryland

The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type 1 recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type 1 IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFNt is a unique type 1 interferon discovered for its role in the animal reproductive cycle. It differs from other type 1 IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFNt has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFNt on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFNt on human cells at high concentrations as well as immunomodulating properties consistent with other type 1 IFNs including an antilymphoproliferative effect and inhibition of IFNg-induced HLA class II expression. These results suggest that OvIFNt could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.

Key Words: mulitple sclerosis • interferons • experimental allergic encephalomylitis • T cells • lymphotoxicity • autoimmune disorders

Multiple Sclerosis, Vol. 4, No. 2, 63-69 (1998)
DOI: 10.1177/135245859800400204


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