Type I interferons as immunoregulatory molecules; implications for therapy in experimental autoimmune uveoretinitis

Arch Immunol Ther Exp (Warsz). 2002;50(4):243-54.

Abstract

Clinical trials have shown that the type I interferon (IFN)-alpha/beta have some beneficial effects on organ-specific autoimmune diseases, such as Behcet's diseases and multiple sclerosis, although the precise mechanisms remain largely unresolved. T helper cells 1 (Th1)-mediated autoimmune responses are involved in the initiation and/or progression of human uveitis, such as Behcet's disease. The animal model of experimental autoimmune uveoretinitis (EAU), characterized by a monophasic clinical course, has contributed to the understanding of the pathogenesis of human uveitis. Th1 producing IFN-gamma induce EAU development, while Th2 producing IL-4/IL-10 prevent the disease. However, depending on the cytokine milieu, the pro-inflammatory cytokine IFN-gamma may attenuate the autoimmune responses and anti-inflammatory cytokine IL-4 exacerbates it. Chemokines also play a crucial role in EAU development, which might be resolved by Th2-mediated immune responses. The administration of IFN-alpha/beta prevents EAU development, accompanied by a diminished production of IFN-gamma/IL-10. Interestingly, however, IFN-alpha/beta also have some beneficial effects on patients with Th2-like phenotype in addition to Th1-like phenotypes. Thus, the immuno-modulatory action of IFN-alpha/beta may be dependent on the context of cytokine combination and/or their concentrations.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / therapy*
  • Clinical Trials as Topic
  • Humans
  • Immunotherapy / methods*
  • Interferon Type I / immunology*
  • Interferon Type I / therapeutic use*
  • Retinitis / drug therapy
  • Retinitis / immunology*
  • Retinitis / therapy*
  • Uveitis / drug therapy
  • Uveitis / immunology*
  • Uveitis / therapy*

Substances

  • Interferon Type I