Cytotoxic T lymphocyte antigen-4 (CTLA4) binds both CD80 and Cd86 and inhibits T lymphocyte activation via CD28. Il-6 is a pleiotropic cytokine that has been associated with many autoimmune conditions including uveitis. Blockade of these molecules by either CTLA4-Ig, a fusion protein of CTLA4 and immunoglobulin, or via an antibody against IL-6, has shown efficacy in conditions such as rheumatoid arthritis. To determine the effect of inhibiting these pathways in uveitis mice were challenged with interphotoreceptor binding protein peptide1-20 to induce experimental autoimmune uveitis (EAU), and CTLA4-Ig or anti-IL-6R was given either during induction phase (same day) or effector phase (seven days after challenge) and disease scores were assessed. The results show that both CTLA4-Ig and anti-IL-6R were effective at reducing clinical scores in animals when given at day zero. However, only CTLA4-Ig was effective at reducing disease when given at day seven when lymphocytes against IRBP1-20 had already been primed. The data was supported by in vitro studies showing that while CTLA4-Ig, but not anti-IL-6R could inhibit proliferation of IRBP1-20 specific T cells. These results show that the effectiveness of targeting different molecules involved in EAU will depend on the temporal kinetics of individual mediators of the immune response. 

CTLA4-Ig suppresses development of experimental autoimmune uveitis in the induction and effector phases: comparison with blockade of interleukin-6.
Iwahashi C, Fujimoto M, Nomura S, et al.
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Graham Wallace

Birmingham and Midland Eye Centre, Birmingham, UK.

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