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Rheumatology Advance Access originally published online on January 22, 2009
Rheumatology 2009 48(4):347-354; doi:10.1093/rheumatology/ken489
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Takeru Yoshimura1,2, Koh-Hei Sonoda1, Nobuyuki Ohguro3, Yoshiyuki Ohsugi4, Tatsuro Ishibashi1, Daniel J. Cua5, Takashi Kobayashi2, Hiroki Yoshida6 and Akihiko Yoshimura2,7

1Department of Ophthalmology, Graduate School of Medical Sciences, 2Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 3Department of Ophthalmology, Osaka University Medical School, Osaka, 4Chugai Pharmaceutical Company Limited, Tokyo, Japan, 5Schering-Plough Biopharma, Palo Alto, CA, USA, 6Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Nabeshima, Saga and 7Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Correspondence to: Koh-Hei Sonoda, Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan. E-mail: sonodak{at}med.kyushu-u.ac.jp


  Abstract

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.

KEY WORDS: Autoimmunity, Cytokine, Eye, IL-6 receptor, Th17

Submitted 12 August 2008; revised version accepted 1 December 2008.
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