Influence of human granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein (PIXY321) on the hematopoietic toxicity associated with anti-viral drugs (zidovudine and didanosine) in vitro using normal human marrow cells.
Influence of human granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein (PIXY321) on the hematopoietic toxicity associated with anti-viral drugs (zidovudine and didanosine) in vitro using normal human marrow cells.
复制标题
使用正常人骨髓细胞体外研究人粒细胞-巨噬细胞集落刺激因子/白细胞介素-3融合蛋白（PIXY321）对与抗病毒药物（齐多夫定和去羟肌苷）相关的造血毒性的影响。
DOI：
10.1016/0024-3205(95)02074-s
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发表时间：
1995
期刊：
影响因子：
6.1
通讯作者：
Hughes,NK
中科院分区：
文献类型：
--
作者：
Gallicchio,VS;Hughes,NK
抗病毒药物去羟肌苷（ddl）和齐多夫定（AZT），合成核苷类似物，已被用于治疗获得性免疫缺陷综合征（AIDS）。虽然齐多夫定（AZT）的临床应用仍然广泛，但它与病毒疾病抗性的发展和对造血系统的毒性有关。为了降低病毒病抗性和血液学毒性的发生率，已经开发了替代的核苷逆转录酶衍生物如去羟肌苷（ddl）。我们在这里报告的研究设计，以评估比较去羟肌苷（ddl）与齐多夫定（AZT）单独使用或与正常的非粘附，T细胞耗竭的人骨髓细胞在存在或不存在的情况下铺板时的毒性概况。人细胞因子粒细胞-巨噬细胞集落刺激因子和白细胞介素-3融合蛋白（PIXY 321）。如预期的，去羟肌苷（ddl）对人造血祖细胞（即CFU-GEMM、CFU-GM、CFU-Meg和BFU-E）的毒性低于齐多夫定。去羟肌苷（ddl）与齐多夫定（AZT）合用时毒性相加。在不存在药物PIXY 321的情况下，培养的所有祖细胞的集落形成增加。在去羟肌苷（ddl）或齐多夫定（AZT）的存在下，无论是作为单一药物还是组合，PDCY 321都显著降低了毒性。这些结果表明，PIXY 321是一种有效的细胞因子，当在体外使用时能够逆转与抗病毒药物相关的毒性，其中去羟肌苷（ddl）的毒性低于齐多夫定（AZT）;然而，当组合时，它们对造血祖细胞的抑制是累加的。
The antiviral drugs didanosine (ddl) and zidovudine (AZT), synthetic nucleoside analogs, have been used in the treatment of acquired immunodeficiency syndrome (AIDS). Although clinical use of zidovudine (AZT) is still widely used, it is associated with the development of virus disease resistance and toxicity to the hematopoietic system. Alternative nucleoside reverse transcriptase derivatives such as didanosine (ddl) have been developed in order to reduce the incidence of virus disease resistance and hematological toxicity. We report here studies designed to evaluate the toxicity profile comparing didanosine (ddl) with zidovudine (AZT) when used alone or in combination with normal non-adherent, T-cell depleted human marrow cells plated in the presence or absence of the. human cytokine fusion protein of granulocyte-macrophage colony stimulating factor and interleukin-3 (PIXY321). As expected, didanosine (ddl) was less toxic for human hematopoietic progenitor Cells, I.e, CFU-GEMM, CFU-GM, CFU-Meg, and BFU-E than zidovudine. Toxicity was additive when didanosine (ddl) and zidovudine (AZT) were combined. In the absence of drugs PIXY321 colony formation was increased for all progenitor cells cultured. In the presence of didanosine (ddl) or zidovudine (AZT), either as single-agents or combined, PDCY321 reduced toxicity significantly. These results demonstrate PIXY321 is an effective cytokine capable of reversing the toxicity associated with anti-viral drugs when used in vitro where didanosine (ddl) is less toxic than zidovudine (AZT); however their suppression of hematopoietic progenitors is additive when combined.