期刊
BLOOD
卷 108, 期 13, 页码 3967-3975出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-04-020610
关键词
-
类别
MRL/lpr mice develop a human lupuslike syndrome and, as in autoimmune lympho-proliferative syndrome (ALPS), massive lymphoproliferation due to inactivation of Fas-mediated apoptosis. Presently, no effective therapy exists for ALPS, and long term, therapies for lupus are hazardous. We show herein that arsenic trioxide (AS(2)O(3)) is able to achieve quasi-total regression of antibody- and cell-mediated manifestations in MRL/lpr mice. AS(2)O(3) activated caspases and eliminated the activated T lymphocytes responsible for lymphoproliferation and skin, lung, and kidney lesions, leading to significantly prolonged survival rates. This treatment also markedly reduced anti-DNA autoantibody, rheumatoid factor, IL-18, IFN-gamma, nitric oxide metabolite, TNF-alpha, Fas ligand, and IL-10 levels and immune-complex deposits in glomeruli. AS(2)O(3) restored cellular reduced glutathione levels, thereby limiting the toxic effect of nitric oxide, which is overproduced in MRL/lpr mice. Furthermore, AS(2)O(3) protected young animals against developing the syndrome and induced almost total disease disappearance in older affected mice, thereby demonstrating that it is a novel promising therapeutic agent for autoimmune diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据