Kotsch Katja, Ulrich Frank, Reutzel-Selke Anja, Pascher Andreas, Faber W, Warnick P, Hoffman S, Francuski M, Kunert C, Kuecuek O, Schumacher G, Wesslau C, Lun A, Kohler S, Weiss S, Tullius S G, Neuhaus P, Pratschke Johann
Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Ann Surg. 2008 Dec;248(6):1042-50. doi: 10.1097/SLA.0b013e318190e70c.
To investigate potential beneficial effects of donor treatment with methylprednisolone on organ function and outcome after liver transplantation.
It is proven experimentally and clinically that the brain death of the donor leads to increased levels of inflammatory cytokines and is followed by an intensified ischemia/reperfusion injury after organ transplantation. In experiments, donor treatment with steroids successfully diminished these effects and led to better organ function after transplantation.
To investigate whether methylprednisolone treatment of the deceased donor is applicable to attenuate brain death-associated damage in clinical liver transplantation we conducted a prospective randomized treatment-versus-control study in 100 deceased donors. Donor treatment (n = 50) consisted of 250 mg methylprednisolone at the time of consent for organ donation and a subsequent infusion of 100 mg/h until recovery of organs. A liver biopsy was taken immediately after laparotomy and blood samples were obtained after brain death diagnosis and before organ recovery. Cytokines were assessed by real-time reverse transcriptase-polymerase chain reaction. Soluble serum cytokines were measured by cytometric bead array system.
After methylprednisolone treatment, steroid plasma levels were significantly higher (P < 0.05), and a significant decrease in soluble interleukins, monocyte chemotactic protein-1, interleukin-2, interleukin-6, tumor necrosis factor-alpha, and inducible protein-10 was observed. Methylprednisolone treatment resulted in a significant downregulation of intercellular adhesion molecule-1, tumor necrosis factor-alpha, major histocompatibility complex class II, Fas-ligand, inducible protein-10, and CD68 intragraft mRNA expression. Significantly ameliorated ischemia/reperfusion injury in the posttransplant course was accompanied by a decreased incidence of acute rejection.
Our present study verifies the protective effect of methylprednisolone treatment in deceased donor liver transplantation, suggesting it as a potential therapeutical approach.
探讨甲基强的松龙对供体进行治疗对肝移植后器官功能及预后的潜在有益作用。
实验和临床已证实，供体脑死亡会导致炎症细胞因子水平升高，进而在器官移植后引发更严重的缺血/再灌注损伤。在实验中，用类固醇对供体进行治疗成功减轻了这些影响，并使移植后器官功能更好。
为了研究甲基强的松龙对已故供体的治疗是否适用于减轻临床肝移植中与脑死亡相关的损伤，我们对100名已故供体进行了一项前瞻性随机治疗对照研究。供体治疗组（n = 50）在同意器官捐赠时给予250 mg甲基强的松龙，随后以100 mg/h的速度持续输注直至器官恢复。剖腹手术后立即进行肝活检，并在脑死亡诊断后和器官恢复前采集血样。通过实时逆转录聚合酶链反应评估细胞因子。用细胞计数珠阵列系统测量可溶性血清细胞因子。
甲基强的松龙治疗后，血浆类固醇水平显著升高（P < 0.05），可溶性白细胞介素、单核细胞趋化蛋白-1、白细胞介素-2、白细胞介素-6、肿瘤坏死因子-α和诱导蛋白-10显著降低。甲基强的松龙治疗导致细胞间黏附分子-1、肿瘤坏死因子-α、主要组织相容性复合体II类、Fas配体、诱导蛋白-10和移植物内CD68 mRNA表达显著下调。移植后过程中缺血/再灌注损伤明显改善，同时急性排斥反应的发生率降低。
我们目前的研究证实了甲基强的松龙治疗在已故供体肝移植中的保护作用，表明它是一种潜在的治疗方法。
