INHIBITION OF IMMUNE FUNCTIONS BY ANTIVIRAL DRUGS
INHIBITION OF IMMUNE FUNCTIONS BY ANTIVIRAL DRUGS
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DOI：
10.1172/jci115217
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发表时间：
1991-06-01
影响因子：
15.9
通讯作者：
FINBERG, RW
中科院分区：
文献类型：
--
作者：
HEAGY, W;CRUMPACKER, C;FINBERG, RW
用抗病毒药物3‘-叠氮-3’-脱氧胸苷(AZT)、利巴韦林、更昔洛韦、2‘3’-二脱氧肌苷(DDI)或阿昔洛韦培养健康人外周血单个核细胞(PBMC)，体外检测其免疫功能。为了确定评估抗病毒药物对免疫细胞影响的方法，通过测量[H-3]胸腺嘧啶核苷和[C-14]亮氨酸掺入、细胞生长、细胞核糖核酸、脱氧核糖核酸和蛋白质水平以及PBMC增殖周期(即从G0-->；G1->；S-->；G2+M)来评估PBMC对丝裂原、ConA或植物血凝素的反应。AZT、利巴韦林或更昔洛韦处理后，细胞周期中G1、S和G2+M期的增殖细胞数、DNA含量和[H-3]胸腺嘧啶核苷摄取均减少。AZT或利巴韦林可减少培养物中的RNA和蛋白质，并抑制细胞生长，但更昔洛韦不能。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的有丝分裂几乎没有影响。抗病毒药物对免疫细胞的抑制作用可能是患者长期使用药物后观察到的免疫恶化的原因之一。
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 [H-3]thymidine and [C-14]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 [H-3]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.