Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in multiple sclerosis and autoimmune disorders.
The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type I recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type I IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFN tau is a unique type I interferon discovered for its role in the animal reproductive cycle. It differs from other type I 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 IFN tau has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFN tau on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFN tau on human cells at high concentrations as well as immunomodulating properties consistent with other type I IFNs including an antilymphoproliferative effect and inhibition of IFN gamma-induced HLA class II expression. These results suggest that OvIFN tau could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.
Khan
O A
OA
Department of Neurology, University of Maryland School of Medicine, Baltimore, USA.
Jiang
H
H
Subramaniam
P S
PS
Johnson
H M
HM
Dhib-Jalbut
S S
SS
D017951:Antigen Presentation / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D004730:Endothelium, Vascular / Q000166:cytology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D015213:Neuroimmunomodulation / Q000502:physiology*; D011257:Pregnancy Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology
D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D011257:Pregnancy Proteins; C020947:interferon tau