The effect of the novel tellurium compound AS101 on autoimmune diseases

被引:62
作者
Halpert, Gilad [1 ]
Sredni, Benjamin [1 ]
机构
[1] Bar Ilan Univ, CAIR Inst, Mina & Everard Goodman Fac Life Sci, Safdie AIDS & Immunol Res Ctr, IL-52900 Ramat Gan, Israel
关键词
Autoimmune diseases; Tellurium; AS101; Integrins; Cytokines; IL-17; REGULATORY T-CELLS; ACTIVE CROHNS-DISEASE; COTTON-TOP TAMARIN; IMMUNOMODULATOR AS101; INTEGRIN ACTIVATION; ADHESION MOLECULES; MULTIPLE-SCLEROSIS; HUMANIZED ANTIBODY; NATALIZUMAB; INHIBITION;
D O I
10.1016/j.autrev.2014.08.003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tellurium is a rare element, which has been regarded as a non-essential trace element despite its relative abundance in the human body. The chemistry of tellurium supports a plethora of activities, but its biochemistry is not clearly established to date. The small tellurium(IV) compound, ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) developed and initially investigated by us, is currently being evaluated in Phase II clinical trials in psoriasis patients. AS101 is the first tellurium compound to be tested for clinical efficacy. This compound is a potent immunomodulator both in vitro and in vivo with a variety of potential therapeutic applications. The present review will focus on the immunomodulatory properties of AS101, and specifically, its effects in mitigating autoimmune diseases. AS101 has several activities that act on the immune system, including: 1) its ability to reduce IL-17 levels and to inhibit the function of Th17 cells; 2) its specific unique redox-modulating activities enabling the inhibition of specific leukocyte integrins such as alpha 4 beta 1 and alpha 4 beta 7, that are pivotal for diapedesis of macrophages and CD4(+) T inflammatory/auto-reactive cells into the autoimmune tissues; and 3) its ability to enhance the activity of regulatory T cells (Treg). These activities coupled with its excellent safety profile suggest that AS101 may be a promising candidate for the management of autoimmune diseases. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:1230 / 1235
页数:6
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