LYMPHOCYTE-SELECTIVE ANTIPROLIFERATIVE AND IMMUNOSUPPRESSIVE EFFECTS OF MYCOPHENOLIC-ACID IN MICE
LYMPHOCYTE-SELECTIVE ANTIPROLIFERATIVE AND IMMUNOSUPPRESSIVE EFFECTS OF MYCOPHENOLIC-ACID IN MICE
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DOI：
10.1111/j.1365-3083.1991.tb03747.x
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发表时间：
1991-02-01
影响因子：
3.7
通讯作者：
ALLISON, AC
中科院分区：
文献类型：
--
作者：
EUGUI, EM;MIRKOVICH, A;ALLISON, AC
霉酚酸（MPA），口服给药小鼠，抑制绵羊红细胞抗体的形成。 MPA还以剂量相关的方式抑制小鼠中针对同种异体细胞的细胞毒性T淋巴细胞的产生，并阻止同种异体细胞的消除。 然而，短期治疗的T淋巴细胞与治疗可达到的剂量的MPA不抑制效应期的细胞毒性。 足以防止小鼠同种异体移植排斥反应的MPA剂量可抑制标记胸苷掺入小鼠淋巴结和脾脏的DNA中，但不抑制睾丸的生殖细胞或空肠的基底上皮细胞中的标记胸苷掺入DNA中;它们不产生中性粒细胞减少症、贫血症或血小板减少症。 这些观察结果表明，MPA在体内具有淋巴细胞选择性抗增殖作用，并且可以抑制细胞介导的和体液免疫应答，而没有主要的副作用。 MPA的优势，目前使用的和最近确定的免疫抑制药物的原因进行了讨论。 所描述的实验系统为药物抑制同种异体移植排斥反应的能力提供了一种方便的体内测定。
Mycophenolic acid (MPA), administered orally to mice, inhibits the formation of antibodies to sheep erythrocytes. MPA also suppresses, in a dose-related manner, the generation of cytotoxic T-lymphocytes against allogeneic cells in mice and prevents the elimination of allogeneic cells. However, short-term treatment of T lymphocytes with therapeutically attainable doses of MPA does not inhibit the effector phase of cytotoxicity. Doses of MPA sufficient to prevent allograft rejection in mice inhibit the incorporation of labelled thymidine into DNA in the lymph nodes and spleen of mice but not in the germinal cells of the testis or in the basal epithelial cells of the jejunum; they do not produce neutropenia, anaemia or thrombocytopenia. These observations show that MPA has lymphocyte-selective anti-proliferative effects in vivo and can inhibit both cell-mediated and humoral immune responses without major side effects. Reasons why MPA has advantages over currently used and recently identified immunosuppressive drugs are discussed. The experimental system described provides a convenient in vivo assay for the capacity of drugs to inhibit allograft rejection.