Saiga K, Toyoda E, Tokunaka K, Masuda A, Matsumoto S, Mashiba H, Kuramochi H, Nemoto K, Abe F, Kawagishi N, Furukawa H, Ono M
Pharmaceutical Group, Nippon Kayaku Co., Ltd, Tokyo, Japan.
Bone Marrow Transplant. 2006 Feb;37(3):317-23. doi: 10.1038/sj.bmt.1705231.
A role for dendritic cells (DCs) has been emphasized in the onset of acute graft-versus-host disease (GVHD). We have made efforts to develop a new strategy for suppression of DC functions with a chemical compound in the treatment of acute GVHD. We here describe the immunological characterization of the new chemical compound NK026680. It was found that NK026680 significantly suppressed (1) expression of CD83, CD86, and major histocompatibility complex (MHC) class I and II antigens on human monocyte-derived DCs, (2) excretion of interleukin-12p40 on activation of monocyte-derived DCs, (3) allogeneic responses of human and mouse T cells and (4) mortality in mice with acute GVHD evoked across MHC class I or II. The beneficial effect of NK026680 administered orally was without any recognizable adverse effects. Early intervention in acute GVHD was required for this effect, indicating that an early event in acute GVHD is a critical target of NK026680. We propose the use of NK026680 as a prophylactic for acute GVHD.
树突状细胞（DCs）在急性移植物抗宿主病（GVHD）的发病过程中的作用已得到重视。我们致力于开发一种新策略，在急性GVHD治疗中使用一种化合物来抑制DC功能。在此，我们描述这种新化合物NK026680的免疫学特性。发现NK026680能显著抑制：（1）人单核细胞来源的DC上CD83、CD86以及主要组织相容性复合体（MHC）I类和II类抗原的表达；（2）单核细胞来源的DC激活时白细胞介素-12p40的分泌；（3）人和小鼠T细胞的同种异体反应；（4）通过MHC I类或II类诱发的急性GVHD小鼠的死亡率。口服NK026680的有益效果没有任何可识别的不良反应。这种效果需要对急性GVHD进行早期干预，表明急性GVHD中的早期事件是NK026680的关键作用靶点。我们建议将NK026680用作急性GVHD的预防药物。
