Jung Florian J, Yang Lin, Härter Luc, Inci Ilhan, Schneiter Didier, Lardinois Didier, Keel Marius, Weder Walter, Korom Stephan
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
J Pineal Res. 2004 Aug;37(1):36-41. doi: 10.1111/j.1600-079X.2004.00133.x.
Melatonin, secreted by the pineal gland, is a multifunctional agent which (i) protects tissues from damage through free radical scavenging and attenuates ischemia/reperfusion injury in organ grafts; (ii) acts synergistically with cellular antioxidants; and (iii) displays complex, dose-dependent immunoenhancing and suppressing effects in vitro and in vivo. We analyzed the immunomodulatory effect of melatonin on acute allograft rejection. Cardiac grafts were transplanted from LBNF1 to LEW rats and anastomosed to the abdominal great vessels. The effect of low-dose (LD; 20 mg/kg/day) and high-dose (HD; 200 mg/kg/day) melatonin treatment in recipients compared with untreated controls was investigated. HD melatonin therapy abrogated acute rejection, significantly prolonging allograft survival (mean survival: 12.3 +/- 1 days S.D., n = 8, P < 0.0001) compared with untreated controls, which rapidly reject the transplant (6.3 +/- 1 days n = 12). LD therapy did not extend survival significantly (7.3 +/- 1.1 days, n = 12). Allospecific IgM showed a significant decrease in animals receiving HD therapy versus untreated recipients at days 10 and 14 post-transplantation (P < 0.01), whereas in the LD group at day 10, a significant increase in allospecific IgM (P < 0.01) over the HD cohort was demonstrated. HD treatment markedly reduced lymphocyte proliferative capacity compared with controls and the LD group. HD melatonin treatment abrogated acute allograft rejection and significantly prolonged graft survival. Our results suggest an involvement of melatonin in humoral and cellular immune pathways following perfused organ transplantation. These findings may indicate a novel therapeutic approach, based on modulation of the neuroendocrine/immune axis through melatonin as a possible future immunosuppressant in organ transplantation.
褪黑素由松果体分泌，是一种多功能物质，它（i）通过清除自由基保护组织，减轻器官移植中的缺血/再灌注损伤；（ii）与细胞抗氧化剂协同作用；（iii）在体外和体内表现出复杂的、剂量依赖性的免疫增强和抑制作用。我们分析了褪黑素对急性同种异体移植排斥反应的免疫调节作用。将心脏移植物从LBNF1大鼠移植到LEW大鼠，并与腹部大血管吻合。研究了低剂量（LD；20mg/kg/天）和高剂量（HD；200mg/kg/天）褪黑素治疗对受体的影响，并与未治疗的对照组进行比较。与迅速排斥移植的未治疗对照组（6.3±1天，n = 12）相比，HD褪黑素治疗消除了急性排斥反应，显著延长了同种异体移植物的存活时间（平均存活时间：12.3±1天标准差，n = 8，P < 0.0001）。LD治疗未显著延长存活时间（7.3±1.1天，n = 12）。在移植后第10天和第14天，接受HD治疗的动物与未治疗的受体相比，同种特异性IgM显著降低（P < 0.01），而在LD组第10天时，同种特异性IgM比HD组显著增加（P < 0.01）。与对照组和LD组相比，HD治疗显著降低了淋巴细胞增殖能力。HD褪黑素治疗消除了急性同种异体移植排斥反应，显著延长了移植物存活时间。我们的结果表明，褪黑素参与了灌注器官移植后的体液和细胞免疫途径。这些发现可能表明一种基于通过褪黑素调节神经内分泌/免疫轴的新型治疗方法，褪黑素可能成为器官移植中未来的免疫抑制剂。
