Corticotropin releasing factor with or without methotrexate for prevention of graft-versus-host disease in DLA-nonidentical unrelated canine marrow grafts.
Corticotropin releasing factor with or without methotrexate for prevention of graft-versus-host disease in DLA-nonidentical unrelated canine marrow grafts.
复制标题
促肾上腺皮质激素释放因子联合或不联合甲氨蝶呤，用于预防 DLA 异种无关犬骨髓移植物中的移植物抗宿主病。
DOI：
10.1097/00007890-199508270-00014
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发表时间：
1995
期刊：
影响因子：
6.2
通讯作者：
Graham,TC
中科院分区：
文献类型：
--
作者：
Yu,C;Storb,R;Braude,I;Deeg,HJ;Schuening,FG;Huss,R;Graham,TC
甲氨蝶呤(MTX)、*环孢菌素和最近的FK506已经成功地单独或联合用于预防犬(1-5)和接受骨髓移植的人类患者(6-8)的急性移植物抗宿主病(GVHD)。虽然这些药物在人类白细胞抗原相合的骨髓移植中相当有效，但在预防供者配型较差的骨髓受者的移植物抗宿主病方面的作用要小得多(9-11)。因此，寻找新的免疫抑制剂的工作一直在继续。我们已经在一个成熟的临床前犬模型中测试了一种这样的药物，促肾上腺皮质激素释放因子(CRF)。CRF是应激反应的主要中枢神经系统调节器(12)。最近的研究表明，CRF在免疫系统中也发挥着重要的作用：CRF调节自然杀伤细胞的细胞毒作用(13，14)；抑制T淋巴细胞的增殖(12，15)；抑制T细胞和跨内皮细胞的迁移(Oppenheimer-Marks N，个人沟通)；阻断物理或化学损伤引起的局部炎症反应(16，17)；以及抑制某些炎症细胞因子的释放，如IL-1，IL-6和干扰素(12，18)。CRF诱导
Methotrexate (MTX),* cyclosporine, and more recently FK506 have been used successfully either alone or in combination to prevent acute graft-versus-host disease (GVHD) in dogs (1-5), and also in human patients (6–8) undergoing marrow transplantation. While quite effective in HLA-identical marrow grafts, the drugs have been considerably less active in preventing GVHD in recipients of marrow from less-well-matched donors (9–11). Therefore, the search for new immunosuppressive agents has continued. We have tested one such agent, corticotropin releasing factor (CRF), in a well-established preclinical canine model. CRF is a major central nervous system regulator for stress responses (12). Recent studies have shown that CRF also plays an important role in the immune system: CRF regulates natural killer cell cytotoxicity (13, 14); inhibits T lymphocyte proliferation (12, 15); inhibits T cell and transendothelial cell migration (Oppenheimer-Marks N, personal communication); blocks local inflammatory reactions induced by physical or chemical damage (16, 17); and suppresses the release of certain inflammatory cytokines such as interleukin-1, interleukin-6, and interferon (12, 18). CRF-induced