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首页> 外文期刊>Journal of inflammation. >Inhibition of allogeneic inflammatory responses by the Ribonucleotide Reductase Inhibitors, Didox and Trimidox
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Inhibition of allogeneic inflammatory responses by the Ribonucleotide Reductase Inhibitors, Didox and Trimidox

机译：核糖核苷酸还原酶抑制剂Didox和Trimidox抑制同种异体炎症反应

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Background Graft-versus-host disease is the single most important obstacle facing successful allogeneic stem cell transplantation (SCT). Even with current immunosuppressive therapies, morbidity and mortality rates are high. Current therapies including cyclosporine A (CyA) and related compounds target IL-2 signaling. However, although these compounds offer great benefit, they are also associated with multiple toxicities. Therefore, new compounds with a greater efficacy and reduced toxicity are needed to enable us to overcome this hurdle. Methods The allogeneic mixed lymphocyte reaction (MLR) is a unique ex vivo method to study a drug's action on the initial events resulting in T-cell activation and proliferation, synonymous to the initial stages of tissue and organ destruction by T-cell responses in organ rejection and Graft-versus-host disease. Using this approach, we examined the effectiveness of two ribonucleotide reductase inhibitors (RRI), Didox and Trimidox, to inhibit T-cell activation and proliferation. Results The compounds caused a marked reduction in the proliferative responses of T-cells, which is also accompanied by decreased secretion of cytokines IL-6, IFN-γ, TNF-α, IL-2, IL-13, IL-10 and IL-4. Conclusions In conclusion, these data provide critical information to justify further investigation into the potential use of these compounds post allogeneic bone marrow transplantation to alleviate graft-versus-host disease thereby achieving better outcomes.
机译：背景移植物抗宿主病是成功进行同种异体干细胞移植（SCT）面临的唯一最重要的障碍。即使采用当前的免疫抑制疗法，发病率和死亡率也很高。当前的疗法包括环孢素A（CyA）和相关化合物靶向IL-2信号传导。然而，尽管这些化合物提供了很大的益处，但是它们还与多种毒性有关。因此，需要具有更高功效和更低毒性的新化合物来使我们克服这一障碍。方法同种异体混合淋巴细胞反应（MLR）是一种独特的离体方法，用于研究药物对导致T细胞活化和增殖的初始事件的作用，这与器官中T细胞反应破坏组织和器官的初始阶段同义排斥反应和移植物抗宿主病。使用这种方法，我们检查了两种核糖核苷酸还原酶抑制剂（RRI）Didox和Trimidox抑制T细胞活化和增殖的有效性。结果这些化合物引起T细胞增殖反应的明显减少，同时还伴随着细胞因子IL-6，IFN-γ，TNF-α，IL-2，IL-13，IL-10和IL的分泌减少。 -4。结论总之，这些数据为进一步研究这些化合物在同种异体骨髓移植后缓解移植物抗宿主病的潜在用途提供了关键信息，从而可以取得更好的结果。

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