Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: in vitro immunosuppressive effects on rat blood and spleen lymphocytes
Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: in vitro immunosuppressive effects on rat blood and spleen lymphocytes
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DOI：
10.1016/s0378-5173(00)00544-5
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发表时间：
2000-10-10
影响因子：
5.8
通讯作者：
Mehvar, R
中科院分区：
文献类型：
--
作者：
Rensberger, KL;Hoganson, DA;Mehvar, R
用伴刀豆球蛋白4（Con-A）刺激淋巴细胞，用淋巴细胞增殖试验检测甲基强的松龙（MP）与右旋糖酐70 kDa（DEX-MPS）偶联物的体外免疫抑制活性。在试验中使用了从无药物雄性Sprague-Dawley大鼠中分离的血液和脾淋巴细胞。首先，确定Con-A刺激淋巴细胞的最佳浓度。然后在存在0.25、0.5、1.0：2.5、5.0、10、20和50 nM浓度（MP当量）的DEX-MPS或游离MP的情况下检测淋巴细胞增殖的抑制。在脾和血淋巴细胞的有丝分裂原浓度分别为2.5和10 μ g/ml时，观察到Con-A对淋巴细胞的最大刺激。对于游离MP，观察到效应（淋巴细胞增殖抑制%）与MP浓度对数之间呈S形关系。此外，血液的最大抑制作用（I-max）和产生半数I-max的MP浓度（IC 50）分别为98%和1.38 nM，脾淋巴细胞的最大抑制作用（I-max）和MP浓度分别为86%和3.1 nM。对于与葡聚糖缀合的MP，响应-对数浓度曲线基本上向右偏移，血液和脾淋巴细胞的IC 50值分别为40和52 nhl。可以得出结论，与游离MPI相比，连接到葡聚糖的类固醇具有最小的免疫抑制活性。因此，为了在体内有效，DEW-MPS应在体内释放MP。(C)2000 Elsevier Science B. V.保留所有权利。
The in vitro immunosuppressive activity of a conjugate of methylprednisolone (MP) with dextran 70 kDa (DEX-MPS) was tested using the lymphocyte proliferation assay after stimulation of lymphocytes with concanavalin 4 (Con-A). Blood and spleen lymphocytes, isolated from drug-free male Sprague-Dawley rats, were used in the assay. First, the optimum concentration of Con-A for stimulation of lymphocytes was determined. The inhibition of the lymphocyte proliferation was then tested in the presence of 0.25, 0.5, 1.0: 2.5, 5.0, 10, 20, and 50 nM concentrations (MP equivalent) of DEX-MPS or free MP. The maximum stimulation of lymphocytes with Con-A was observed at mitogen concentrations of 2.5 and 10 mug/ml for the spleen and blood lymphocytes, respectively. For free MP, sigmoidal relationships were observed between the effect (% inhibition of lymphocyte proliferation) and the logarithm of MP concentration. Additionally, the maximum inhibitory effect (I-max) and MP concentration producing half of I-max (IC50) were, respectively, 98% and 1.38 nM For the blood and 86% and 3.1 nM for the spleen lymphocytes. For MP conjugated to dextran, the response-log concentration curves were substantially shifted to the right with IC50 values of 40 and 52 nhl for the blood and spleen lymphocytes, respectively. It is concluded that compared with free MPI the steroid attached to dextran has minimal immunosuppressive activity. Therefore, to be effective in vivo, DEW-MPS should release MP in the body. (C) 2000 Elsevier Science B.V. All rights reserved.