Fraternale A, Casabianca A, Tonelli A, Chiarantini L, Brandi G, Magnani M
Istituto di Chimica Biologia G. Fornaini, University of Urbino, Via Saffi, 2, 61029-Urbino, Italy.
Eur J Clin Invest. 2001 Mar;31(3):248-52. doi: 10.1046/j.1365-2362.2001.00806.x.
The failure of highly active antiretroviral therapies (HAART) is mainly due to the existence of latent infected reservoirs, such as macrophages and resting CD4+ T cells. In this paper, we report the results that we obtained in a murine model of AIDS by alternating the administration of the lympholitic drug 2-Fluoro-ara-AMP (Fludarabine) to eliminate the infected cells, with that of Azidothymidine (AZT) plus reduced glutathione (GSH) encapsulated in erythrocytes, to protect lymphocytes and macrophages not yet infected, respectively. Two groups of infected mice were treated as follows: one group was treated by alternating the administration of Fludarabine and AZT (treatment A), while the other group received the same treatment plus GSH-loaded erythrocytes given with AZT (treatment A + L-RBC). Fludarabine was administered intraperitoneally, AZT in the drinking water and GSH was encapsulated in erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. The results obtained show that GSH-loaded erythrocytes provide additive effects in all the parameters examined. Alternation of a lympholitic drug and antiretroviral drug is effective in reducing the progression of murine AIDS. Addition of a system to protect macrophages provides additive effects in almost all the parameters considered, confirming that combination therapies aimed at protecting different infectable cell compartments are better than treatments protecting mainly lymphocytes.
高效抗逆转录病毒疗法（HAART）的失败主要归因于潜伏感染库的存在，如巨噬细胞和静息CD4 + T细胞。在本文中，我们报告了在艾滋病小鼠模型中获得的结果，即通过交替给予淋巴细胞溶解药物2-氟阿糖腺苷（氟达拉滨）以消除感染细胞，与给予包裹在红细胞中的叠氮胸苷（AZT）加还原型谷胱甘肽（GSH），分别保护尚未感染的淋巴细胞和巨噬细胞。两组感染小鼠接受如下治疗：一组通过交替给予氟达拉滨和AZT进行治疗（治疗A），而另一组接受相同治疗并在给予AZT时加用负载GSH的红细胞（治疗A + L-RBC）。氟达拉滨通过腹腔注射给药，AZT通过饮水给药，GSH通过低渗透析和等渗重封程序包裹在红细胞中。所获得的结果表明，负载GSH的红细胞在所有检测参数中均具有累加效应。淋巴细胞溶解药物和抗逆转录病毒药物的交替使用可有效减缓小鼠艾滋病的进展。添加保护巨噬细胞的系统在几乎所有考虑的参数中均具有累加效应，证实旨在保护不同可感染细胞区室的联合疗法优于主要保护淋巴细胞的治疗方法。
