Kutza J, Hayes M P, Clouse K A
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20852, USA.
AIDS. 1998 May 28;12(8):F59-64. doi: 10.1097/00002030-199808000-00001.
To determine the effect of recombinant human interleukin (IL)-2 on HIV-1 replication and macrophage colony stimulating factor (M-CSF) production by HIV-1-infected monocyte-derived macrophages (MDM).
Therapeutic use of IL-2 increases the number and function of CD4+ T cells. IL-2 also increases M-CSF production and M-CSF receptor expression by human monocytes, but the subsequent effects on HIV-1 replication in MDM have yet to be determined. MDM from HIV-1-seronegative donors were cultured in the presence and absence of IL-2 and infected with HIV-1. Harvested supernatants were monitored for reverse transcriptase activity and M-CSF production.
Reverse transcriptase activity was significantly lower when MDM cultures were treated with IL-2 for 10 days prior to infection with HIV-1. IL-2 did not stimulate production of inhibitory chemokines or cytokines, but FACS analysis revealed that expression of CD4, the primary HIV-1 receptor, and CC-chemokine receptor-5, a coreceptor used by macrophage-tropic viruses, are down modulated after treatment with IL-2.
IL-2 may not only be of benefit in restoring immune function in AIDS patients, but may also help to prevent the infection of healthy macrophages by decreasing their expression of HIV-1 receptors.
确定重组人白细胞介素(IL)-2 对 HIV-1 感染的单核细胞衍生巨噬细胞(MDM)中 HIV-1 复制及巨噬细胞集落刺激因子(M-CSF)产生的影响。
IL-2 的治疗性应用可增加 CD4+T 细胞的数量和功能。IL-2 还可增加人单核细胞的 M-CSF 产生及 M-CSF 受体表达,但对 MDM 中 HIV-1 复制的后续影响尚未确定。将来自 HIV-1 血清阴性供体的 MDM 在有或无 IL-2 的情况下培养,并感染 HIV-1。监测收获的上清液中的逆转录酶活性及 M-CSF 产生情况。
在感染 HIV-1 之前用 IL-2 处理 MDM 培养物 10 天时,逆转录酶活性显著降低。IL-2 未刺激抑制性趋化因子或细胞因子的产生,但流式细胞术分析显示,主要的 HIV-1 受体 CD4 及巨噬细胞嗜性病毒使用的共受体 CC 趋化因子受体 5 的表达在用 IL-2 处理后下调。
IL-2 不仅可能有助于恢复艾滋病患者的免疫功能,还可能通过降低健康巨噬细胞的 HIV-1 受体表达来帮助预防其感染。