Caballero F, Pelegrí C, Castell M, Franch A, Castellote C
Unit of Physiology, Faculty of Pharmacy, University of Barcelona, Spain.
Immunopharmacology. 1998 May;39(2):83-91. doi: 10.1016/s0162-3109(98)00011-3.
Although anti-CD4 monoclonal antibodies (MoAb) have been proven successful in preventing or treating adjuvant arthritis, little is known about the duration of the effects of these MoAb and their pharmacokinetics. In this work, we report the effects of a mouse anti-rat CD4 MoAb, named W3/25, on peripheral blood lymphocytes from female Wistar rats. Animals received a single dose of W3/25, from 1 to 3 mg, and blood was sampled at different time points from 0 h to 15 days after MoAb administration. After erythrocyte lysis, samples were stained by indirect immunofluorescence and analyzed by flow cytometry. Pharmacokinetic data were studied by assessing plasma levels of mouse IgG1 by ELISA-sandwich. W3/25 produced the down-regulation of surface CD4 molecule as early as 20 min after its administration at doses of 2 and 3 mg. The same effect was seen 30 min after a dose of 1 mg. The recovery of lymphocytes with normal expression of CD4 also depended of the dose administered. Thus, CD4+ lymphocytes were recovered at 48, 72 and 96 h in rats treated with 1, 2 or 3 mg of W3/25, respectively. Plasma levels of free antibody were detectable from 20 min to 72 h, 60 min to 48 h and 60 min to 24 h after administration of 3, 2 and 1 mg, respectively, of W3/25. The mouse IgG1 MoAb used in this study followed a two-compartment model and its behavior was linear.
尽管抗CD4单克隆抗体（MoAb）已被证明在预防或治疗佐剂性关节炎方面是成功的，但对于这些MoAb的作用持续时间及其药代动力学却知之甚少。在这项研究中，我们报告了一种名为W3/25的小鼠抗大鼠CD4 MoAb对雌性Wistar大鼠外周血淋巴细胞的影响。动物接受1至3毫克的单剂量W3/25，并在给予MoAb后0小时至15天的不同时间点采集血液。红细胞裂解后，样品通过间接免疫荧光染色并通过流式细胞术进行分析。通过ELISA夹心法评估小鼠IgG1的血浆水平来研究药代动力学数据。W3/25在以2毫克和3毫克剂量给药后20分钟就产生了表面CD4分子的下调。在给予1毫克剂量后30分钟也观察到了相同的效果。CD4正常表达的淋巴细胞的恢复也取决于给药剂量。因此，分别用1毫克、2毫克或3毫克W3/25处理的大鼠在48小时、72小时和96小时恢复了CD4 +淋巴细胞。分别在给予3毫克、2毫克和1毫克W3/25后20分钟至72小时、60分钟至48小时和60分钟至24小时可检测到游离抗体的血浆水平。本研究中使用的小鼠IgG1 MoAb遵循双室模型，其行为呈线性。
