Blanco J, Cabrera C, Jou A, Ruiz L, Clotet B, Esté J A
Institut de Recerca de la SIDA-Caixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain.
AIDS. 1999 Apr 1;13(5):547-55. doi: 10.1097/00002030-199904010-00003.
To evaluate changes in serum levels of chemokines, chemokine production, and chemokine receptor expression by peripheral blood mononuclear cells (PBMC), after treatment of HIV-1-infected individuals with interleukin (IL)-2.
We determined CC-chemokine levels by enzyme-linked immunosorbent assay and chemokine receptor expression using FACS analysis or reverse transcriptase polymerase chain reaction in samples from patients receiving highly active antiretroviral therapy (HAART) supplemented with low doses of recombinant IL-2. Results were compared with a control group of patients receiving HAART.
Serum levels of RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and the production of these chemokines by unstimulated and stimulated PBMC, were not modified by IL-2 administration. In contrast, the IL-2-treated group showed increased expression of CXC-chemokine receptor (CXCR)-4 in the CD4 T-cell subset after 24 weeks of treatment, which was associated with increased mRNA levels. A lower increase was observed in CC-chemokine receptor (CCR)-5 expression by CD4 T cells. No modifications in the expression of these receptors were observed in monocytes and no general increases were observed in mRNA levels of chemokine receptors CCR-1, CCR-2b and CCR-3 in IL-2-treated patients.
IL-2 at doses that significantly increase CD4 cell counts does not induce dramatic modifications in the chemokine/chemokine receptor system. Only expression of CXCR-4 appears to increase, due in part to lymphocyte activation. Therefore, the efficacy of IL-2 treatment in HIV-1 infection has to be evaluated by its ability to activate and induce faster regeneration of the immune system.
评估白细胞介素(IL)-2治疗人类免疫缺陷病毒1型(HIV-1)感染个体后,趋化因子血清水平、趋化因子产生以及外周血单个核细胞(PBMC)趋化因子受体表达的变化。
我们采用酶联免疫吸附测定法测定CC趋化因子水平,并通过流式细胞术分析或逆转录聚合酶链反应,检测接受高活性抗逆转录病毒疗法(HAART)并补充低剂量重组IL-2患者样本中的趋化因子受体表达。将结果与接受HAART的对照组患者进行比较。
RANTES、巨噬细胞炎性蛋白(MIP)-1α和MIP-1β的血清水平,以及未刺激和刺激后的PBMC产生的这些趋化因子,均未因给予IL-2而改变。相比之下,IL-2治疗组在治疗24周后,CD4 T细胞亚群中CXC趋化因子受体(CXCR)-4的表达增加,这与mRNA水平升高有关。CD4 T细胞中CC趋化因子受体(CCR)-5的表达升高幅度较小。在单核细胞中未观察到这些受体表达的变化,且在接受IL-2治疗的患者中,趋化因子受体CCR-1、CCR-2b和CCR-3的mRNA水平也未普遍升高。
显著增加CD4细胞计数的剂量的IL-2不会引起趋化因子/趋化因子受体系统的显著改变。似乎只有CXCR-4的表达增加,部分原因是淋巴细胞活化。因此,必须通过其激活和诱导免疫系统更快再生的能力,来评估IL-2治疗HIV-1感染的疗效。