Heagy W, Crumpacker C, Lopez P A, Finberg R W
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
J Clin Invest. 1991 Jun;87(6):1916-24. doi: 10.1172/JCI115217.
Immune functions were evaluated in vitro for PBMC isolated from healthy donors and cultured with the antiviral agents, 3'-azido-3'-deoxythymidine (AZT), ribavirin, ganciclovir, 2'3'-dideoxyinosine (ddI), or acyclovir. To identify methods for assessing the effects of antiviral drugs on immune cells, the PBMC response to mitogens, Con A, or phytohemagglutinin was evaluated from measurements of [3H]thymidine and [14C]-leucine incorporation, cell growth, cellular RNA, DNA, and protein levels, and the PBMC proliferative cycle (i.e., progression from G0----G1----S----G2 + M). At clinically relevant concentrations, AZT, ribavirin, or ganciclovir diminished PBMC responsiveness to mitogen. The numbers of proliferating cells in G1, S, and G2 + M phases of the cell cycle, DNA content, and [3H]thymidine uptake were decreased in cultures treated with AZT, ribavirin, or ganciclovir. AZT or ribavirin but not ganciclovir reduced RNA and protein in the cultures and inhibited cell growth. Whereas AZT, ribavirin, or ganciclovir were antiproliferative, ddI or acyclovir had little, if any, effect on PBMC mitogenesis. The inhibitory effects of antivirals on immune cells may contribute to the immune deterioration observed in patients following prolonged use of the drugs.
从健康供体分离出外周血单核细胞（PBMC），并与抗病毒药物3'-叠氮-3'-脱氧胸苷（AZT）、利巴韦林、更昔洛韦、2'3'-双脱氧肌苷（ddI）或阿昔洛韦一起培养，以此在体外评估免疫功能。为了确定评估抗病毒药物对免疫细胞作用的方法，通过测量[3H]胸腺嘧啶核苷和[14C] - 亮氨酸掺入、细胞生长、细胞RNA、DNA和蛋白质水平以及PBMC增殖周期（即从G0→G1→S→G2 + M的进程）来评估PBMC对丝裂原、刀豆蛋白A或植物血凝素的反应。在临床相关浓度下，AZT、利巴韦林或更昔洛韦会降低PBMC对丝裂原的反应性。用AZT、利巴韦林或更昔洛韦处理的培养物中，细胞周期G1、S和G2 + M期的增殖细胞数量、DNA含量和[3H]胸腺嘧啶核苷摄取量均减少。AZT或利巴韦林而非更昔洛韦会降低培养物中的RNA和蛋白质水平并抑制细胞生长。虽然AZT、利巴韦林或更昔洛韦具有抗增殖作用，但ddI或阿昔洛韦对PBMC有丝分裂几乎没有影响（如果有影响的话也很小）。抗病毒药物对免疫细胞的抑制作用可能导致患者长期使用这些药物后出现免疫功能恶化。
