Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a history of immune restoration disease after HAART.
Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a history of immune restoration disease after HAART.
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DOI：
10.1046/j.1464-2662.2001.00096.x
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发表时间：
2002-01-01
期刊：
影响因子：
3
通讯作者：
French, M A
中科院分区：
文献类型：
--
作者：
Stone, S F;Price, P;French, M A
目的：我们之前描述了与无症状机会性感染相关的免疫恢复疾病（IRD），该感染出现在对高效抗逆转录病毒治疗（HAART）有反应的免疫缺陷艾滋病毒患者中。在这里，我们解决了有 IRD 病史的患者是否表现出持续免疫激活的问题，具体表现为白细胞介素 (IL)-6 和可溶性 IL-6 受体 (sIL-6R) 水平升高。 方法：从 CD4 T 细胞计数最低值 < 80/μL 的 HIV 患者中收集外周血单核细胞 (PBMC) 和血浆，这些患者在 HAART 后已实现免疫重建，接受过 (n=14) 或未接受过 (n=15) 治疗的患者IRD，CD4 T 细胞/μL < 80 个的严重免疫缺陷 (SID) 患者 (n=8) 和 HIV 血清阴性对照 (n=15)。通过酶联免疫吸附测定 (ELISA) 测量 PBMC 的产量以及 IL-6、sIL-6R 和干扰素 (IFN)-gamma（仅 PBMC）的血浆水平。使用细胞内流式细胞术确定 HIV 患者和对照中 IL-6 的主要细胞来源。结果：来自 IRD 患者的未刺激 PBMC 产生的 IL-6 和 sIL-6R 含量显着高于非 IRD 患者和 HIV 血清阴性对照。与非 IRD 患者相比，IRD 患者经丝裂原刺激的 PBMC 上清液中 sIL-6R 浓度也显着更高。 IRD 和非 IRD 患者的 IFN-γ 产生没有差异。与非 IRD 患者、SID 患者和对照相比，IRD 患者血浆 IL-6 水平显着升高。单核细胞是 HIV 患者和对照中 IL-6 的主要来源。结论：HAART 后有 IRD 病史的患者 IL-6 和 sIL-6R 水平升高。
OBJECTIVES: We have previously described immune restoration diseases (IRD) associated with asymptomatic opportunistic infections presenting in immunodeficient HIV patients responding to highly active antiretroviral therapy (HAART). Here we address the question of whether patients with a history of IRD exhibit persistent immune activation, shown by elevated levels of interleukin-(IL)-6 and soluble IL-6 receptor (sIL-6R).METHODS: Peripheral blood mononuclear cells (PBMCs) and plasma were collected from HIV patients with nadir CD4 T cell counts of < 80/microL and who had achieved immune reconstitution after HAART with (n=14) or without (n=15) experiencing IRD, severely immunodeficient (SID) patients with < 80 CD4 T cells/microL (n=8) and HIV seronegative controls (n=15). PBMC production and plasma levels of IL-6, sIL-6R and interferon (IFN)-gamma (PBMC only) were measured by enzyme linked immunosorbent assay (ELISA). Intracellular flow cytometry was used to determine the predominant cellular source of IL-6 in HIV patients and controls.RESULTS: Unstimulated PBMC from IRD patients produced significantly higher amounts of IL-6 and sIL-6R than non-IRD patients and HIV seronegative controls. The sIL-6R concentration was also significantly higher in supernatants from mitogen-stimulated PBMC from IRD patients compared to non-IRD patients. The production of IFN-gamma did not differ between IRD and non-IRD patients. IRD patients had significantly higher plasma levels of IL-6 compared to non-IRD patients, SID patients and controls. Monocytes were the predominant source of IL-6 in both HIV patients and controls.CONCLUSIONS: Patients with a history of IRD after HAART have elevated levels of IL-6 and sIL-6R.