Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Science and Technology Unit, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Molecules. 2021 Jul 12;26(14):4237. doi: 10.3390/molecules26144237.
Systemic steroids are used to treat acute graft-versus-host disease (aGVHD) caused by allogenic bone marrow transplantation (allo-BMT); however, their prolonged use results in complications. Hence, new agents for treating aGVHD are required. Recently, a new compound A (CpdA), with anti-inflammatory activity and reduced side effects compared to steroids, has been identified. Here, we aimed to determine whether CpdA can improve the outcome of aGVHD when administered after transplantation in a mouse model (C57BL/6 in B6D2F1). After conditioning with 9Gy total body irradiation, mice were infused with bone marrow (BM) cells and splenocytes from either syngeneic (B6D2F1) or allogeneic (C57BL/6) donors. The animals were subsequently treated (3 days/week) with 7.5 mg/kg CpdA from day +15 to day +28; the controls received 0.9% NaCl. Thereafter, the incidence and severity of aGVHD in aGVHD target organs were analyzed. Survival and clinical scores did not differ significantly; however, CpdA-treated animals showed high cell infiltration in the target organs. In bulk mixed lymphocyte reactions, CpdA treatment reduced the cell proliferation and expression of inflammatory cytokines and chemokines compared to controls, whereas levels of TNF, IL-23, chemokines, and chemokine receptors increased. CpdA significantly reduced proliferation in vitro but increased T cell infiltration in target organs.
系统性类固醇被用于治疗异基因骨髓移植（allo-BMT）引起的急性移植物抗宿主病（aGVHD）；然而，其长期使用会导致并发症。因此，需要新的药物来治疗 aGVHD。最近，一种新的化合物 A（CpdA）被发现具有抗炎活性，且副作用比类固醇低。在这里，我们旨在确定 CpdA 在同种异体（C57BL/6 至 B6D2F1）小鼠模型中移植后是否可以改善 aGVHD 的预后。在 9Gy 全身照射预处理后，小鼠输注来自同基因（B6D2F1）或同种异体（C57BL/6）供体的骨髓（BM）细胞和脾细胞。然后，动物从第 +15 天到第 +28 天接受 7.5mg/kg CpdA 治疗（每周 3 次）；对照组接受 0.9%NaCl。此后，分析 aGVHD 靶器官的发病率和严重程度。aGVHD 靶器官的存活率和临床评分无显著差异；然而，CpdA 治疗组动物显示出靶器官中有高细胞浸润。在混合淋巴细胞反应中，与对照组相比，CpdA 治疗降低了细胞增殖和炎症细胞因子和趋化因子的表达，而 TNF、IL-23、趋化因子和趋化因子受体的水平增加。CpdA 显著降低了体外的增殖，但增加了靶器官中的 T 细胞浸润。
