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Baoying Liu, Zhiyu Li, Phyllis Silver, Cuiyan Tan, Ping Chen, Chi-Chao Chan, Robert B Nussenblatt; Effect of HDACi Givinostat in Treating Experimental Ocular Autoimmunity. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):882.
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Histone deacetylase inhibitor (HDACi) Givinostat, also called ITF2357, binds the zinc-containing catalytic domain of the HDAC and potentially has anti-inflammatory, anti-angiogenic and anti-neoplastic activities. Givinostat has been shown to inhibit expression of tumor necrosis factor-α, interferon γ, interleukin 1α and β and interleukin 6. It is currently in 11 phase II clinical trials and has been designated an orphan drug for the treatment of juvenile idiopathic arthritis in the European Union. In this study, we aim to examine the effect of Givinostat in treating experimental ocular autoimmunity.
Experimental autoimmune uveitis (EAU) was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP; 100 μg) in CFA. Treatment with Givinostat was by twice a week intraperitoneal injection of 0.2 mg. Disease severity was assessed by both fundoscopy and histological examination. Draining lymph node cells were tested for proliferation by thymidine uptake. In addition, the intracellular expression of cytokines and Foxp3 was determined by flow cytometry.
Treatment with Givinostat efficiently inhibited the development of EAU in mice, as well as the cellular proliferation immune responses against IRBP. Givinostat treatment moderately increased the proportion of Foxp3 expressing T-regulatory cells. However, preliminary results indicated that the treatment exhibited little effect on the expression of the signature cytokines of Th1 and Th17 subpopulations, IFN-gamma and IL-17.
Givinostat, a histone deacetylase inhibitor, efficiently inhibits EAU development and related cellular immune responses. Givinostat may be considered for treatment of pathogenic immunity in humans.
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