Makonkawkeyoon S, Limson-Pobre R N, Moreira A L, Schauf V, Kaplan G
Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5974-8. doi: 10.1073/pnas.90.13.5974.
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 clinical setting to inhibit both virus replication and the TNF-alpha-induced systemic toxicity of HIV-1 and opportunistic infections.
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）细胞系中潜伏的人类免疫缺陷病毒1型（HIV-1）的激活。这种抑制作用呈剂量依赖性，且在细胞暴露于重组TNF-α、佛波酯肉豆蔻酸酯、脂多糖和其他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产生减少。在佛波酯肉豆蔻酸酯和重组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作用。沙利度胺的存在还抑制了17例晚期HIV-1感染和艾滋病患者中16例患者外周血单核细胞中的病毒激活。这些结果表明，在临床环境中使用沙利度胺可抑制病毒复制以及TNF-α诱导的HIV-1全身毒性和机会性感染。
