Weiss L, Haeffner-Cavaillon N, Gilquin J, Kazatchkine M D
Unité d'Immunopathologie, INSERM U28, Hôpital Broussais, Paris, France.
AIDS. 1990 Mar;4(3):255-7. doi: 10.1097/00002030-199003000-00013.
Zidovudine (AZT) penetrates human monocytes to exert its antiretroviral activity at the level of reverse transcriptase in infected cells. Stimulation of normal human monocytes with lipopolysaccharide (LPS) results in the transcription of interleukin-1 (IL-1) genes, the intracellular accumulation of IL-1 alpha and IL-1 beta precursors, and the subsequent extracellular release of functional IL-1 beta. The present study demonstrates that zidovudine inhibits the extracellular release of IL-1 activity without affecting the generation of intracellular IL-1 or the amount of released IL-1 beta protein. Similar results were observed with monocytes from normal individuals and monocytes from patients with AIDS. Since IL-1 may upregulate the expression of HIV genes in infected cells, the inhibitory effect of zidovudine on the release of functional IL-1 may be relevant for the beneficial effect of the drug in HIV infection.
齐多夫定（AZT）可穿透人类单核细胞，在受感染细胞的逆转录酶水平发挥其抗逆转录病毒活性。用脂多糖（LPS）刺激正常人单核细胞会导致白细胞介素-1（IL-1）基因转录、IL-1α和IL-1β前体在细胞内积累以及随后功能性IL-1β的细胞外释放。本研究表明，齐多夫定可抑制IL-1活性的细胞外释放，而不影响细胞内IL-1的产生或释放的IL-1β蛋白量。在正常个体的单核细胞和艾滋病患者的单核细胞中观察到了类似结果。由于IL-1可能上调受感染细胞中HIV基因的表达，齐多夫定对功能性IL-1释放的抑制作用可能与该药物在HIV感染中的有益作用相关。
