Ammonium tri-chloro(dioxoethylene-O,O′-)tellurate (AS-101), an anti–IL-10 compound, is a nontoxic immunomodulator.
AS101 (0.5-2.5 μg/ml) decreased IL-10 production in a dose-dependent manner. Incubation of RMCL and RMC in the presence of AS101 gradually and significantly decreased mesangial cell proliferation [1]. AS101 (0.5 μg/ml, 1 μg/ml) decreased tyrosine phosphorylation and nuclear translocation of stat3 via inhibition of IL-10 [2]. AS-101 induced proliferation and IL-2 production by human lymphocytes and enhanced the production of IL-2 and colony-stimulating factor by mouse spleen cells. Systemically administration of AS-101 to mice mediated antitumour effects. AS-101 directly enhanced the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS patients [3]. AS101 showed significant bone marrow (BM)-sparing effects and preventd hair loss in chemotherapy-treated patients, with minimal overall toxicity [4]. In mice subjected to cecal ligation and puncture (CLP), treatment with AS101 significantly increased survival of septic mice. AS101 treatment restored the ability of these cells to secrete TNF-α and IL-1β. AS101 increased class II Ag expression on peritoneal macrophages. AS101 increased the level of IFN-γ secreted by splenocytes [5].
References:
[1] Kalechman Y, Sredni B, Weinstein T, et al. Production of the novel mesangial autocrine growth factors GDNF and IL-10 is regulated by the immunomodulator AS101[J]. Journal of the American Society of Nephrology, 2003, 14(3): 620-630.
[2] Kalechman Y, Gafter U, Weinstein T, et al. Inhibition of Interleukin-10 by the Immunomodulator AS101 Reduces Mesangial Cell Proliferation in Experimental Mesangioproliferative Glomerulonephritis ASSOCIATION WITH DEPHOSPHORYLATION OF STAT3[J]. Journal of Biological Chemistry, 2004, 279(23): 24724-24732.
[3] Sredni B, Caspi R R, Klein A, et al. A new immunomodulating compound (AS-101) with potential therapeutic application[J]. Nature, 1987, 330(6144): 173-176.
[4] Sredni B, Albeck M, Tichler T, et al. Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide[J]. Journal of Clinical Oncology, 1995, 13(9): 2342-2353.
[5] Kalechman Y, Gafter U, Gal R, et al. Anti-IL-10 therapeutic strategy using the immunomodulator AS101 in protecting mice from sepsis-induced death: dependence on timing of immunomodulating intervention[J]. The Journal of Immunology, 2002, 169(1): 384-392.