Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis

Rheumatology (Oxford). 2009 Apr;48(4):347-54. doi: 10.1093/rheumatology/ken489. Epub 2009 Jan 22.


Objectives: Human endogenous uveitis is one of the sight-threatening diseases associated with variety of systemic disorders, such as Behcet's disease and sarcoidosis. Recently, biosynthesized antibodies against inflammatory cytokines have been recognized to be useful to control the regional inflammation. In this study, we focused on the possibility of IL-6-based biological therapies for endogenous uveitis. We initially confirmed the significant increase of several inflammatory soluble factors including IL-6 in the vitreous fluids from refractory/chronic engogenous uveitis patients.

Methods: To investigate the role of IL-6 in the formation of refractory ocular inflammation, we used the mouse experimental autoimmune uveitis (EAU) model. Both IL-6 and IL-23 are required for the development of IL-17-producing helper T subset (Th17) from naïve CD4(+) T cells. Results. In the EAU model, neither IL-6-deficient mice nor IL-23-deficient mice could induce Th17 cells and the EAU score was decreased in these mice in the entire time course. We also confirmed that systemic administration of anti-il-6 receptor antibody ameliorates EAU By suppressing both systemic and regional TH17 responses.

Conclusions: IL-6 is responsible for causing ocular inflammation, and it is, at least partially, due to IL-6-dependent Th17 differentiation. IL-6 may be a target for therapy of refractory endogenous uveitis in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / therapeutic use
  • Aqueous Humor / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-23 / genetics
  • Interleukin-23 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Receptors, Interleukin-6 / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Treatment Outcome
  • Uveitis / immunology*
  • Uveitis / therapy*
  • Vitreous Body / immunology


  • Antibodies
  • Interleukin-17
  • Interleukin-23
  • Interleukin-6
  • Receptors, Interleukin-6