Purchase this article with an account.
H. Haruta, S. Hohki, H. Mashimo, N. Hashida, Y. Saishin, N. Ohguro, Y. Tano, T. Naka; Effect of Anti-Interleukin-6 Receptor Monoclonal Antibody in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):820.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
A novel subset of interleukin (IL)-17-producing CD4+ T helper cells (Th17) is thought to play a pivotal role in experimental autoimmune uveitis (EAU) and human uveitis. Recent studies also have indicated that IL-6 promotes Th17 differentiation in vitro. The aim of this study is to investigate the effect of anti-IL-6 receptor monoclonal antibody (IL-6RmAb) treatment on T-helper differentiation in EAU.
EAU was induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in C57BL/6 female mice. The mice received one injection of 8 mg of IL-6RmAb or isotype control IgG (rat IgG1) by intraperitoneal injection on day 0, 1, or 5 after IRBP immunization. The clinical scores of EAU and T-helper differentiation in these mice were analyzed. All mice were treated according to the ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.
EAU development was significantly suppressed in mice treated with IL-6RmAb on day 0 or day 1; however, in mice treated with IL-6RmAb on day 5, the clinical score of EAU was comparable to that in control mice. Immunization with IRBP predominantly increased the frequency of Th17 cells in the cervical lymph nodes rather than Th1 cells. The start of Th17 differentiation was observed on day 3 after IRBP immunization. Treatment of EAU with IL-6RmAb on day 0 or day 1 markedly suppressed induction of Th17 cells; however, that on day 5 did not. The proportion of Th1 cells did not change significantly as the result of IL-6RmAb treatment.
This study showed that the protective effect of IL-6 blockade in EAU correlated with the inhibition of Th17 differentiation. In addition, because IL-6 blockade after the start of Th17 differentiation did not suppress subsequent Th17 differentiation, this suggested that IL-6 plays an essential role in initiating Th17 differentiation in EAU.
This PDF is available to Subscribers Only