Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of autoimmune encephalomyelitis by oral glatiramer acetate.
IFN-tau, a novel type I IFN that possesses immunomodulatory properties, lacks toxicity normally associated with other type I IFNs. We examined the effects of oral IFN-tau alone and in combination with oral glatiramer acetate in experimental allergic encephalomyelitis (EAE). By comparison of oral administration of IFN-alpha, -beta, and -tau to myelin basic protein-specific TCR-transgenic mice, we demonstrate these type I IFNs promote secretion of the Th2 cytokine IL-10 with similar efficiency. Whereas IFN-alpha and -beta induced IFN-gamma secretion, a Th1 cytokine, IFN-tau did not. Oral IFN-tau alone suppressed EAE. When suboptimal doses were administered orally in combination to wild-type mice, IFN-tau and glatiramer acetate had a synergistic beneficial effect in suppression of EAE. This combination was associated with TGF-beta secretion and enhanced IL-10 production. Thus, IFN-tau is a potential candidate for use as a single agent or in combination therapy for multiple sclerosis.
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jeanne M
JM
Soos
Olaf
O
Stüve
Sawsan
S
Youssef
Manuel
M
Bravo
Howard M
HM
Johnson
Howard L
HL
Weiner
Scott S
SS
Zamvil
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007370:Interferon Type I / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage*; D011257:Pregnancy Proteins / Q000008:administration & dosage*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; D011257:Pregnancy Proteins; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta; C020947:interferon tau; C405722:myelin basic protein 1-11; D016753:Interleukin-10; D000068717:Glatiramer Acetate