title: The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity.
abstract: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease if the central nervous system (CNS). Recently, the type I IFN, IFN-beta-1b was demonstrated to be a useful immunotherapy for MS. During treatment with IFN-beta-1b, toxicity at higher doses has been observed. IFN-tau, discovered for its role in the reproductive cycle, possesses all of the functions normally ascribed to the type I IFNs but lacks the toxicity normally associate with IFN treatment in vitro. We have examined the effects of IFN-tau treatment on experimental allergic encephalomyelitis (EAE), an animal model useful for the study of MS. EAE is a model of Ag-induced autoimmunity that can be modulated by bacterial superantigen to resemble the relapsing-remitting pattern of autoimmune disease observed in MS. IFN-tau was able to prevent development of EAE as effectively as IFN-beta but without associated toxicity such as lymphocyte suppression and weight loss. In addition, IFN-tau was able to prevent superantigen reactivation of EAE akin to the reduction in disease exacerbations observed in IFN-beta-1b treated MS patients. Mechanisms by which IFN-tau may prevent EAE include reduced proliferation in response to the autoantigen myelin basic protein and reduced TNF-alpha production. Thus, IFN-tau may prove to be a promising new IFN therapy for MS in light of its ability to prevent EAE and the lack of toxicity exhibited by this novel IFN.
authors.affiliation: Department of Microbiology, University of Florida, Gainesville 32611, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Soos
authors.forename: P S
authors.initials: PS
authors.lastname: Subramaniam
authors.forename: A C
authors.initials: AC
authors.lastname: Hobeika
authors.forename: J
authors.initials: J
authors.lastname: Schiffenbauer
authors.forename: H M
authors.initials: HM
authors.lastname: Johnson
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D007370:Interferon Type I / Q000494:pharmacology* / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000187:drug effects / Q000276:immunology; D011257:Pregnancy Proteins / Q000494:pharmacology* / Q000633:toxicity*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012756:Sheep; D018089:Superantigens / Q000187:drug effects* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D007370:Interferon Type I; D004676:Myelin Basic Protein; D011257:Pregnancy Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C020947:interferon tau