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用米托蒽醌抑制同种异体反应性的诱导。

Inhibition of the induction of alloreactivity with mitoxantrone.

作者信息

Wang B S, Lumanglas A L, Silva J, Ruszala-Mallon V M, Durr F E

出版信息

Int J Immunopharmacol. 1986;8(8):967-73. doi: 10.1016/0192-0561(86)90099-8.

DOI:10.1016/0192-0561(86)90099-8
PMID:2948926
Abstract

A clinically active anticancer agent, mitoxantrone (MX): 1, 4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9, 10-anthracenedione dihydrochloride, was studied for its potential inhibitory effect on alloreactivity induction. Addition of MX to mixed lymphocyte cultures (MLC) not only inhibited the proliferative response of lymphocytes to alloantigens but also prevented the generation of cytolytic T lymphocytes (CTL). MX showed a long-lasting effect in vitro and acted at the inductive rather than the effector phase of the CTL response as indicated by its failure to alter the activity of those CTL already generated in MLC. MX also inhibited CTL induction in mice. However, the precursors of CTL appeared to be spared in these animals as supported by limiting dilution analysis and also because CTL could be reactivated by exposure of splenocytes to the same or different alloantigens in MLC. The present findings demonstrate that MX is a potent immunosuppressive agent and as such might prove to be clinically useful in the treatment of autoimmune diseases or find utility in the organ transplantation field.

摘要

一种临床活性抗癌药物米托蒽醌(MX):1,4 - 二羟基 - 5,8 - 双[[2 - [(2 - 羟乙基)氨基]乙基]氨基] - 9,10 - 蒽二酮二盐酸盐,被研究其对同种异体反应诱导的潜在抑制作用。将MX添加到混合淋巴细胞培养物(MLC)中,不仅抑制了淋巴细胞对同种异体抗原的增殖反应,还阻止了细胞毒性T淋巴细胞(CTL)的产生。MX在体外显示出持久的作用,并且作用于CTL反应的诱导期而非效应期,这一点由其未能改变MLC中已产生的那些CTL的活性所表明。MX也抑制小鼠体内的CTL诱导。然而,通过有限稀释分析支持,并且也因为在MLC中脾细胞暴露于相同或不同的同种异体抗原时CTL可以被重新激活,CTL的前体在这些动物中似乎未受影响。目前的研究结果表明,MX是一种有效的免疫抑制剂,因此可能在自身免疫性疾病的治疗中证明具有临床实用性,或者在器官移植领域找到用途。

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Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.米托蒽醌诱导继发进展型多发性硬化症患者自然杀伤细胞成熟。
PLoS One. 2012;7(6):e39625. doi: 10.1371/journal.pone.0039625. Epub 2012 Jun 29.
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Mitoxantrone: a review of its use in multiple sclerosis.
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