Combined treatment of glatiramer acetate and low doses of immunosuppressive drugs is effective in the prevention of graft rejection
Combined treatment of glatiramer acetate and low doses of immunosuppressive drugs is effective in the prevention of graft rejection
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DOI：
10.1016/j.intimp.2004.09.007
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发表时间：
2005-01-01
影响因子：
5.6
通讯作者：
Arnon, R
中科院分区：
文献类型：
--
作者：
Aharoni, R;Yussim, A;Arnon, R
免疫调节剂醋酸格拉替雷（GA，共聚物1，Copaxone. GLAT）。目前用于治疗多发性硬化症，是一种具有高安全性的耐受性良好的药物。我们以前已经证明，GA抑制免疫排斥反应表现在移植物抗宿主病，以及在移植物排斥。为了减少目前免疫抑制方案的剂量和毒性，我们现在已经测试了GA的能力。联合低剂量的环孢素（CyA）或他克莫司（FK 506），抑制不匹配的同种异体移植物的排斥反应。我们在此报告，这种联合治疗在几种动物模型中是有效的：（1）它导致小鼠皮肤排斥反应的剧烈过程的显著延迟，表现为皮肤移植物存活的明显延长（高于用至少两倍剂量的免疫抑制药物单独获得的存活）。(2)与单独使用每种药物相比，联合治疗有效抑制了小鼠甲状腺移植物的功能恶化，表现为移植甲状腺的碘吸光度增加了2.2- 20.1倍。(3)联合用药可明显抑制大鼠血管化心脏移植排斥反应。因此，心脏移植物的存活率与GA和低剂量的CyA的组合治疗后的生存时间比通过单独的四倍高剂量的CyA获得的生存时间更长。所有的移植系统。GA与CyA或FK 506的联合治疗显著抑制了移植物排斥，并且比单独用GA或免疫抑制药物的治疗更有效，这表明这种治疗可能有益于人类移植（C）2004 Elsevier B. V.保留所有权利。
The immunomodulator glatiramer acetate (GA, copolymer 1, Copaxone. GLAT). currently used for the treatment of multiple sclerosis, is a well-tolerated drug with a high safety profile. We have previously demonstrated that GA suppressess the immune rejection manifested in graft versus host disease, as well as in graft rejection. In an attempt to reduce the dosage and toxicity of the current immunosuppressive regimens, we have now tested the ability of GA. combined with low closes of cyclosporin (CyA) or tacrolimus (FK506), to suppress the rejection of mismatched allografts across major histocompatibility barriers. We report herewith that such combination therapy was effective in several animal models: (1) it led to a significant delay of the vigorous process of skin rejection in mice, manifested by evidential prolongation in skin graft survival (higher than that obtained with at least double dose of the immunosuppressive drug alone). (2) The combined treatment led to efficient inhibition of the functional deterioration of thyroid grafts in mice, manifested by 2.2- to 20.1-fold increase in iodine absorbance of the transplanted thyroids, as compared to each drug alone. (3) Combination therapy inhibited significantly the rejection of vascularized heart transplants in rats. Thus, cardiac allograft survival following the combined treatment with GA and low dose of CyA was longer than the survival obtained by fourfold higher dose of CyA alone. In all transplantation systems. combination therapy of GA with either CyA or FK506 significantly suppressed graft rejection and was more effective than treatment with either GA or the immunosuppressive drug alone, suggesting that such treatment may be beneficial for human transplantation (C) 2004 Elsevier B.V. All rights reserved.