Grant S C, Lamb W R, Yonan N, Hutchinson I V, Brenchley P E
Department of Cardiology, Wythenshawe Hospital, Manchester, UK.
Transplantation. 1995 Oct 15;60(7):684-9. doi: 10.1097/00007890-199510150-00012.
It is accepted that antithymocyte globulin (ATG) preparations vary in their bioactivity and side effects. However, this is poorly documented in the literature. We compared the clinical course and cytokine response of heart transplant patients who had received either Merieux or Stanford ATG preparations. The serum cytokine response (interleukin [IL]-6, tumor necrosis factor [TNF]-alpha, IL-4, and IL-10) of 28 consecutive heart transplant recipients was measured for 14 days after surgery using ELISAs. The effect of various ATG preparations on cytokine stimulation of whole blood in vitro was also evaluated. There was a much greater in vivo IL-6 and TNF-alpha response to Merieux than to Stanford ATG (P < 0.0005). There was little IL-4 or IL-10 response with either preparation. No side effects could be attributed to either treatment. No significant difference was seen in the frequency of rejection at 30, 90, or 365 days. More infection episodes occurred in the group treated with Stanford ATG at 30 days (0.5 compared with 0.2 episodes/patient; P = 0.097), 90 days (1.2 compared with 0.5 episodes/patient; P = 0.17), and 365 days (2.8 compared with 1.8; P = 0.59), although none of these differences were statistically significant. When tested in vitro for cytokine stimulation, the in vivo pattern was confirmed, with Merieux ATG producing greater levels of TNF-alpha and IL-6 than Stanford ATG. The differences in cytokine stimulation may be reflected in different immunosuppressive activities. Further research to elucidate the important components of immunosuppressive activity while excluding potentially detrimental effects is important.
人们公认抗胸腺细胞球蛋白(ATG)制剂的生物活性和副作用存在差异。然而,这在文献中记载甚少。我们比较了接受美罗华(Merieux)或斯坦福(Stanford)ATG制剂的心脏移植患者的临床病程和细胞因子反应。使用酶联免疫吸附测定法(ELISA)对28例连续心脏移植受者术后14天的血清细胞因子反应(白细胞介素[IL]-6、肿瘤坏死因子[TNF]-α、IL-4和IL-10)进行了检测。还评估了各种ATG制剂对体外全血细胞因子刺激的作用。与斯坦福ATG相比,美罗华ATG在体内引起的IL-6和TNF-α反应要大得多(P<0.0005)。两种制剂引起的IL-4或IL-10反应都很小。两种治疗均未发现副作用。在30天、90天或365天时,排斥反应的发生率没有显著差异。在30天(每位患者0.5次发作对比0.2次发作;P = 0.097)、90天(每位患者1.2次发作对比0.5次发作;P = 0.17)和365天(2.8次对比1.8次;P = 0.59)时,接受斯坦福ATG治疗的组中感染发作更多,尽管这些差异均无统计学意义。在体外进行细胞因子刺激测试时,体内模式得到证实,美罗华ATG产生的TNF-α和IL-6水平高于斯坦福ATG。细胞因子刺激的差异可能反映在不同的免疫抑制活性上。进一步开展研究以阐明免疫抑制活性的重要成分,同时排除潜在的有害影响,这很重要。