Comparison of the in vitro antiproliferative effects of five immunosuppressive drugs on lymphocytes in whole blood from cats
Comparison of the in vitro antiproliferative effects of five immunosuppressive drugs on lymphocytes in whole blood from cats
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DOI：
10.2460/ajvr.2000.61.906
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发表时间：
2000-08-01
影响因子：
1
通讯作者：
Craigmill, AL
中科院分区：
文献类型：
--
作者：
Kyles, AE;Gregory, CR;Craigmill, AL
目的-比较环孢菌素和4种新型免疫抑制药物对从健康猫收集的全血中的淋巴细胞的体外免疫抑制作用。样品群体-从10只健康成年家猫收集的全血样品。程序-在与和不与各种浓度的环孢菌素、他克莫司、西罗莫司、霉酚酸（MPA），或A771726通过使用[H-3]胸苷掺入来测量。计算导致50%抑制丝裂原诱导的增殖的药物浓度（IC_（50）），使用台盼蓝染料排除法测定淋巴细胞活力。用伴刀豆球蛋白A测定的平均IC 50为：环孢素46 nM、他克莫司9 nM、西罗莫司12 nM、MPA 16 nM和A771726 30 mM，而用美洲商陆促分裂原测定的平均IC 50为：环孢素33 nM、他克莫司5 nM、西罗莫司15 nM、麦考酚酸14 nM和A771726 25 mM。无论评估哪种药物，有丝分裂原刺激和非刺激的淋巴细胞仍然存活。结论和临床相关性-他克莫司、西罗莫司、MPA和A771726以剂量依赖性方式抑制体外有丝分裂原刺激的猫淋巴细胞增殖。这些新型免疫抑制药物可能有助于管理免疫介导的炎症性疾病以及预防和治疗接受器官移植的猫的排斥反应。
Objective - To compare the in vitro immunosuppressive effects of cyclosporine and 4 novel immunosuppressive drugs on lymphocytes in whole blood collected from healthy cats.Sample Population - Whole blood samples collected from 10 healthy adult domestic shorthair cats.Procedure - Mitogen-stimulated lymphocyte proliferation in whole blood incubated with and without various concentrations of cyclosporine, tacrolimus, sirolimus, mycophenolic acid (MPA), or A771726 was measured by use of [H-3]thymidine incorporation. Drug concentrations that resulted in a 50% inhibition of mitogen-induced proliferation (IC50) were calculated, Lymphocyte viability was determined by use of the trypan blue dye exclusion method.Results-An obvious dose-response relationship for the antiproliferative effects of each drug was detected. Mean IC50 determined with concanavalin A was 46 nM for cyclosporine, 9 nM for tacrolimus, 12 nM for sirolimus, 16 nM for MPA, and 30 mM for A771726, whereas with pokeweed mitogen, mean IC50 was 33 nM for cyclosporine, 5 nM for tacrolimus, 15 nM for sirolimus, 14 nM for mycophenolic acid, and 25 mM for A771726. Mitogen-stimulated and nonstimulated lymphocytes remained viable, regardless of drug evaluated.Conclusions and Clinical Relevance - Tacrolimus, sirolimus, MPA, and A771726 inhibited in vitro mitogen-stimulated proliferation of feline lymphocytes in a dose-dependent manner. These novel immunosuppressive drugs may be useful for management of immune-mediated inflammatory diseases and prevention and treatment of rejection in cats that undergo organ transplantation.