Monotherapy with LF 15-0195, an analogue of 15-deoxyspergualin, significantly prolongs renal allograft survival in monkeys.
Monotherapy with LF 15-0195, an analogue of 15-deoxyspergualin, significantly prolongs renal allograft survival in monkeys.
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LF 15-0195（15-脱氧精胍菌素的类似物）单药治疗可显着延长猴子同种异体移植肾的存活时间。
DOI：
10.1097/01.tp.0000062841.89728.cf
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Zhong,Robert
中科院分区：
文献类型：
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作者：
Yang,Hongji;Chen,Gang;Kanai,Nobuyuki;Shum,Jeffrey;Garcia,Bertha;Huang,Xuyan;Min,Weiping;Luo,Yigang;Dutartre,Patrick;Zhong,Robert
背景：LF 15-0195是一种新型的、更有效的、毒性更小的15-脱氧精胍菌素类似物，15-脱氧精胍菌素是一种用于预防器官移植排斥反应的免疫抑制剂。本研究旨在确定LF 15-0195单药治疗是否能预防非人灵长类动物模型中的肾移植排斥反应。方法：在研究组中，接受者接受LF 15-0195单药治疗，剂量为0.065 mg/kg/天（第2组，n= 4），0.13 mg/kg/天（第3组，n= 4）或0.2 mg/kg/天（第4组，n= 4），在术后0 - 14天皮下给药。结果：第1组由未处理的对照受体组成，术后平均存活6.5±0.6天，均发生晚期排斥反应。LF 15-0195处理显著延长了组2、3和4中的移植物存活，分别延长至20±20天、49±5天和39±4天。在LF 15-0195处理期间，第3组和第4组动物未表现出排斥反应的证据。LF 15-0195停药后，动物维持稳定的肾功能2周，但在5 - 6周时逐渐发生排斥反应。病理学研究表明，与对照标本相比，LF 15-0195处理的同种异体移植物中血管移植物排斥反应减弱。这些组在给药期间也表现出淋巴细胞计数的一过性降低，在LF 15-0195停药后2周恢复至正常水平。LF 15-0195治疗结束时（术后第14天），IgM和IgG的总血清浓度分别平均降低20.4%和31.4%。LF 15-0195未显著改变血小板计数或血红蛋白水平。尸检研究表明，在心脏，肝脏，脾脏，肠，胃，或colon.Conclusions药物毒性的证据。LF 15-0195单药治疗显着延长猴肾移植存活。这些令人鼓舞的数据表明，这种新的代理可能是未来的价值，在临床移植。
Background.LF 15-0195 is a novel, more potent, and less toxic analogue of 15-deoxyspergualin, an antibiotic used as an immunosuppressive agent to prevent rejection of organ transplants. This study was undertaken to determine whether LF 15-0195 monotherapy would prevent renal allograft rejection in a nonhuman primate model.Methods.In the study groups, recipients received LF 15-0195 monotherapy at doses of 0.065 mg/kg per day (group 2, n= 4), 0.13 mg/kg per day (group 3, n= 4), or 0.2 mg/kg per day (group 4, n= 4), administered subcutaneously, on postoperative days 0 to 14.Results.Group 1 consisted of untreated control recipients, all of which developed advanced graft rejection after surviving for an average of 6.5±0.6 days. LF 15-0195 treatment significantly prolonged graft survival in groups 2, 3, and 4, to 20±20 days, 49±5 days, and 39±4 days, respectively. Animals in groups 3 and 4 demonstrated no evidence of rejection during LF 15-0195 treatments. The animals maintained stable renal function for 2 weeks after LF 15-0195 withdrawal but gradually developed rejection at 5 to 6 weeks. Pathologic studies demonstrated that vascular graft rejection was attenuated in LF 15-0195-treated allografts, compared with control specimens. These groups also demonstrated transient reductions in lymphocyte counts during treatment, which returned to normal levels 2 weeks after LF 15-0195 withdrawal. Total serum concentrations of IgM and IgG decreased by a mean of 20.4% and a mean of 31.4%, respectively, at the end of LF 15-0195 treatment (postoperative day 14). LF 15-0195 did not significantly alter thrombocyte counts or hemoglobin levels. Necropsy studies showed no evidence of drug toxicity in the heart, liver, spleen, intestines, stomach, or colon.Conclusions.LF 15-0195 monotherapy significantly prolonged renal allograft survival in monkeys. These encouraging data suggest that this novel agent may be of future value in clinical transplantation.