Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis.
OBJECTIVE
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.
Yoshimura
Takeru
T
Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Sonoda
Koh-Hei
KH
Ohguro
Nobuyuki
N
Ohsugi
Yoshiyuki
Y
Ishibashi
Tatsuro
T
Cua
Daniel J
DJ
Kobayashi
Takashi
T
Yoshida
Hiroki
H
Yoshimura
Akihiko
A
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001082:Aqueous Humor / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D019947:Receptors, Interleukin-6 / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016896:Treatment Outcome; D014605:Uveitis / Q000276:immunology* / Q000628:therapy*; D014822:Vitreous Body / Q000276:immunology
D000906:Antibodies; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D019947:Receptors, Interleukin-6