Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of autoimmune encephalomyelitis by oral glatiramer acetate

J Immunol. 2002 Sep 1;169(5):2231-5. doi: 10.4049/jimmunol.169.5.2231.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Oral
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Drug Synergism
  • Drug Therapy, Combination
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Glatiramer Acetate
  • Immunosuppressive Agents / administration & dosage*
  • Interferon Type I / administration & dosage*
  • Interleukin-10 / metabolism
  • Mice
  • Mice, Transgenic
  • Myelin Basic Protein / immunology
  • Peptide Fragments / immunology
  • Peptides / administration & dosage*
  • Pregnancy Proteins / administration & dosage*
  • Receptors, Antigen, T-Cell / genetics
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Immunosuppressive Agents
  • Interferon Type I
  • Myelin Basic Protein
  • Peptide Fragments
  • Peptides
  • Pregnancy Proteins
  • Receptors, Antigen, T-Cell
  • Transforming Growth Factor beta
  • interferon tau
  • myelin basic protein 1-11
  • Interleukin-10
  • Glatiramer Acetate