THALIDOMIDE INHIBITS THE REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
THALIDOMIDE INHIBITS THE REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
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DOI：
10.1073/pnas.90.13.5974
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发表时间：
1993-07-01
影响因子：
11.1
通讯作者：
KAPLAN, G
中科院分区：
文献类型：
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作者：
MAKONKAWKEYOON, S;LIMSONPOBRE, RNR;KAPLAN, G
沙利度胺是肿瘤坏死因子α（TNF-α）合成的选择性抑制剂，可抑制单核细胞样（U1）细胞系中潜伏性人类免疫缺陷病毒1型（HIV-1）的活化。抑制是剂量依赖性的，并且在细胞暴露于重组TNF-α、佛波醇肉豆蔻酸酯乙酸酯、脂多糖和其它细胞因子组合后发生。与HIV-1抑制相关的是激动剂诱导的TNF-α蛋白和mRNA产生的减少。在佛波醇肉豆蔻酸酯乙酸酯和重组TNF-α刺激的T细胞系ACH-2中未观察到沙利度胺对病毒复制的抑制。沙利度胺的存在也抑制了17例晚期HIV-1感染和AIDS患者中16例外周血单核细胞中病毒的活化。这些结果表明，沙利度胺在临床环境中的使用，以抑制病毒复制和TNF-α诱导的HIV-1和机会性感染的全身毒性。
Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, suppresses the activation of latent human immunodeficiency virus type 1 (HIV-1) in a monocytoid (U1) line. The inhibition is dose dependent and occurs after exposure of the cells to recombinant TNF-alpha, phorbol myristate acetate, lipopolysaccharide, and other cytokine combinations. Associated with HIV-1 inhibition is a reduction in agonist-induced TNF-alpha protein and mRNA production. Thalidomide inhibition of virus replication in the phorbol myristate acetate- and recombinant TNF-alpha-stimulated T-cell line ACH-2 is not observed. The presence of thalidomide also inhibits the activation of virus in the peripheral blood mononuclear cells of 16 out of 17 patients with advanced HIV-1 infection and AIDS. These results suggest the use of thalidomide in a dinical setting to inhibit both virus replication and the TNF-alpha-induced systemic toxicity of HIV-1 and opportunistic infections.