Vila L M, Ríos-Olivares E, Vila S, Ríos Z, Rivera E, Robles R, Reyes J C, Castillo X
Department of Microbiology and Immunology, Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico, USA.
Cell Mol Biol (Noisy-le-grand). 1997 Nov;43(7):981-8.
Activation of CD4+ cells is a prerequisite for infection by the human immunodeficiency virus (HIV). Thus, any agent capable of suppressing CD4+ cell proliferation could create a refractory stage that would impede viral infection. We have reported, in a previous publication, that a biological response modifier (BRM), polyantigenic immunomodulator (PAI) substantially reduces HIV-1 titer (from 20 to 100%) in peripheral mononuclear cells (PBMC) cultures with high viral titer (p24 = 10(2)-10(5) pg/ml). We are presenting data suggesting that the reported reduction in virus titer seems to be associated with a suppressive activity of PAI on the proliferation of PBMC from intravenous drug users (IVDU) infected and non-infected with HIV-1. PAI, a well characterized BRM, is a mixture of inactivated bacterial and influenza virus vaccines. PBMC from healthy donors and IVDU individuals were exposed to PAI, phytohemagglutinin (PHA), interleukin-2 (IL-2) and to combinations of PAI with either PHA or IL-2. Appropriate controls were included. 3H-thymidine pulsing was used as indicator of cell proliferation. The stimulation index and the difference between mean cpm of test sample and control were used to measure proliferative activity. There was a low proliferative response in the PBMC cultures from IVDU and HIV-1 positive patients, but it was substantially lower in the later group. When PBMC cultures from the same group of individuals were exposed to PAI, PHA and IL-2, and to the combination of either PAI plus PHA or IL-2, the response observed in the PAI treated group was uniformly lower than in the other treated cultures. Moreover, when PAI was combined with PHA, it exerted a significant reduction in the measured parameters. The effect of PAI on IL-2 activity was negligible. A suppressive effect of a PAI has been detected on the proliferation of PBMC from IVDA and HIV-1 positive individuals. This activity may be associated with the capacity of PAI to reduce HIV titers in infected PBMC cultures.
CD4+细胞的激活是人类免疫缺陷病毒（HIV）感染的前提条件。因此，任何能够抑制CD4+细胞增殖的药物都可能产生一个难治阶段，从而阻碍病毒感染。我们在之前的一篇出版物中报道，一种生物反应调节剂（BRM），即多抗原免疫调节剂（PAI），能使外周血单个核细胞（PBMC）培养物中高病毒滴度（p24 = 10² - 10⁵ pg/ml）的HIV-1滴度大幅降低（20%至100%）。我们提供的数据表明，所报道的病毒滴度降低似乎与PAI对感染和未感染HIV-1的静脉吸毒者（IVDU）的PBMC增殖的抑制活性有关。PAI是一种特征明确的BRM，是灭活细菌疫苗和流感病毒疫苗的混合物。来自健康供体和IVDU个体的PBMC分别暴露于PAI、植物血凝素（PHA）、白细胞介素-2（IL-2）以及PAI与PHA或IL-2的组合中。设置了适当的对照。使用³H-胸腺嘧啶脉冲作为细胞增殖的指标。刺激指数以及测试样品与对照的平均每分钟计数（cpm）之差用于测量增殖活性。IVDU和HIV-1阳性患者的PBMC培养物中的增殖反应较低，但后一组更低。当同一组个体的PBMC培养物暴露于PAI、PHA和IL-2以及PAI加PHA或IL-2的组合时，PAI处理组中观察到的反应始终低于其他处理的培养物。此外，当PAI与PHA联合使用时，它使测量参数显著降低。PAI对IL-2活性的影响可忽略不计。已检测到PAI对IVDA和HIV-1阳性个体的PBMC增殖有抑制作用。这种活性可能与PAI降低感染的PBMC培养物中HIV滴度的能力有关。
