Langrehr Jan M, Gube Kathrin, Hammer Markus H, Lehmann Manfred, Polenz Dietrich, Pascher Andreas, Volk Hans-Dieter, Reinke Petra
Department of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin Berlin Campus Virchow-Klinikum, Humboldt-Universität zu Berlin, Berlin, Germany.
Transplantation. 2007 Sep 15;84(5):639-46. doi: 10.1097/01.tp.0000280552.85779.d7.
Despite improved immunosuppression, intestinal transplantation is still complicated by severe rejection episodes. To further improve immunosuppressive concepts, we evaluated an anti-CD4 antibody and an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody for their immunosuppressive efficacy in the standard rat model of intestinal transplantation.
Intestinal transplantation was performed in the DA to Lewis combination, and recipients were treated perioperatively with either the anti-CD4 antibody RIB5/2 (day -1, 0, postoperative days 1, 2, 4, 7, 10, 14, 17, and 21), the anti-TNF antibody etanercept (60 min before reperfusion, postoperative days 3, 6, and 9) or a combination of both. Survival, histology and expression of immunologic mediator genes on days 3 and 4 after transplantation were investigated.
Treatment with anti-CD4 antibody alone (19.71+/-5.94) and the antibody combination (171.58+/-122.76) prolonged survival. The chemokine MIP-1alpha was significantly decreased in both anti-CD4 antibody treatment groups, possibly indicating an additional effect of the TNF-alpha blockade on the immune modulation by RIB5/2.
Our study demonstrated long-term graft survival in short-term treatment with a combination of an anti-CD4 antibody and a TNF-alpha antibody in more than 50% of the recipients of intestinal grafts. Such a combined approach could also be useful in clinical small bowel transplantation.
尽管免疫抑制有所改善，但肠道移植仍因严重排斥反应而复杂化。为进一步改进免疫抑制方案，我们在标准大鼠肠道移植模型中评估了一种抗CD4抗体和一种抗肿瘤坏死因子（TNF）-α单克隆抗体的免疫抑制效果。
进行DA到Lewis组合的肠道移植，受体在围手术期接受抗CD4抗体RIB5/2（术前第-1天、0天，术后第1天、2天、4天、7天、10天、14天、17天和21天）、抗TNF抗体依那西普（再灌注前60分钟，术后第3天、6天和9天）或两者联合治疗。研究移植后第3天和第4天的生存率、组织学及免疫介质基因表达。
单独使用抗CD4抗体（19.71±5.94）和抗体联合治疗（171.58±122.76）均延长了生存期。在两个抗CD4抗体治疗组中趋化因子MIP-1α均显著降低，这可能表明TNF-α阻断对RIB5/2的免疫调节有额外作用。
我们的研究表明，在超过50%的肠道移植受体中，抗CD4抗体和TNF-α抗体联合进行短期治疗可实现长期移植物存活。这种联合方法在临床小肠移植中可能也有用。
