Type I interferons as immunoregulatory molecules; implications for therapy in experimental autoimmune uveoretinitis.
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.
Mizuguchi
Junichiro
J
Department of Immunology, Tokyo Medical University, Japan. mizu@tokyo-med.ac.jp
Takeuchi
Masaru
M
Usui
Masahiko
M
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007370:Interferon Type I / Q000276:immunology* / Q000627:therapeutic use*; D012173:Retinitis / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*
D007370:Interferon Type I