Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis

Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis
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DOI:
10.1128/iai.67.3.1251-1260.1999
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发表时间:
1999-03-01
影响因子:
3.1
通讯作者:
Tiemessen, CT
Tiemessen, CT
中科院分区:
医学2区
文献类型:
--
作者:
Meddows-Taylor, S;Martin, DJ;Tiemessen, CT

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在四个研究组中监测体内白细胞介素-8(IL-8)的产生:正常献血者、肺结核(TB)患者、人类免疫缺陷病毒1型(HIV-1)感染患者和双重感染(HIV/TB)患者。我们发现,虽然有证据表明健康个体外周细胞中可检测到细胞相关IL-8(mRNA和蛋白质)水平,但在所研究的疾病状态中,这在很大程度上丢失了。与此同时,在HIV-1感染者伴或不伴肺结核患者中,IL-8的循环水平显著升高(P < 0.001)。另一方面,HIV-1和TB患者(P < 0.05)以及许多HIV/TB组的外周血单个核细胞体外自发产生IL-8的能力增强,但与正常供体相比,它们对各种刺激,特别是植物血凝素的相应反应能力显著降低(P < 0.05)。一组HIV/TB患者外周血IL-8水平与外周血中性粒细胞(PMN)百分比呈显著正相关(r = 0.65; P = 0.01),IL-8受体A(IL-8 RA)表达的比例(r = 0.86; P < 0.01)和表达IL-8 RB(r = 0.77; P < 0.01)的PMN,以及PMN对IL-8作为趋化因子的迁移能力(r = 0.68; P < 0.01)。IL-8 RB荧光强度与血浆IL-8水平呈负相关(r = -0.73; P < 0.01)。我们的研究结果表明,HIV-1中IL-8调节的改变可能对抗菌防御和正常免疫过程具有重要意义。
Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0.01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes.