Daikh D I, Wofsy D
Department of Medicine, Department of Veterans Affairs Medical Center and the University of California, San Francisco, CA 94121, USA.
J Immunol. 2001 Mar 1;166(5):2913-6. doi: 10.4049/jimmunol.166.5.2913.
Cyclophosphamide (CTX) prevents progression of nephritis and prolongs survival in (NZB x NZW)F(1) (B/W) mice and is used to treat humans with lupus nephritis. To compare the efficacy of CTLA4Ig with CTX and determine whether there is an incremental benefit to combining CTLA4Ig with CTX, we treated B/W mice with CTX, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all groups. In mice with advanced renal disease, treatment with both agents reduced proteinuria in 71% of mice, whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice treated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolonging survival of B/W mice with advanced nephritis. This striking reversal of proteinuria is unprecedented in animal models of SLE.
环磷酰胺（CTX）可预防（新西兰黑鼠×新西兰白鼠）F1（B/W）小鼠的肾炎进展并延长其生存期，且被用于治疗狼疮性肾炎患者。为比较CTLA4Ig与CTX的疗效，并确定将CTLA4Ig与CTX联合使用是否有额外益处，我们用CTX、CTLA4Ig或两种药物治疗B/W小鼠。在患有轻度肾病的小鼠中，治疗延迟了蛋白尿的出现并延长了所有组的生存期。在患有晚期肾病的小鼠中，两种药物联合治疗使71%的小鼠蛋白尿减少，而单独使用任何一种药物治疗的小鼠则无此改善。两种药物联合治疗的小鼠生存期也显著改善。因此，CTX与CTLA4Ig联合治疗在减轻晚期肾炎B/W小鼠的肾脏疾病和延长生存期方面比单独使用任何一种药物更有效。这种蛋白尿的显著逆转在系统性红斑狼疮动物模型中是前所未有的。
