González-Nicolás J, Resino S, Jiménez J L, Alvarez S, Fresno M, Muñoz-Fernández M A
Departamento de Inmunología, Hospital General Universitario "Gregorio Marañón", C/ Doctor Esquerdo 46, 28007 Madrid, Spain.
Eur Cytokine Netw. 2001 Jul-Sep;12(3):437-44.
We performed a cross-sectional study to investigate the plasma TNF-alpha and nitric oxide (NO) production in 44 vertically HIV-1-infected children, and the relationship with immunological status and viral replication. As a control group, 36 healthy, uninfected children were studied. Plasma TNF-alpha and NO levels were determined by ELISA. Viral load was quantified using standard assays. Cell proliferation, apoptosis and viral replication were evaluated in vitro by incorporation of (3H)-thymidine, flow cytometry and p24 antigen, respectively. Higher plasma TNF-alpha and NO levels were observed in HIV-1-infected children compared with healthy controls. We found a very strong correlation between plasma TNF-alpha and NO levels in HIV-1-infected children (r = 0.98; p < 0.001). Moreover, HIV-1-infected children with higher viral load (> 4.7 log10) showed higher TNF-alpha and NO levels than those with viral load below this threshold. Interestingly, we detected inducible nitric oxide synthase (iNOS) mRNA in T-lymphocytes from HIV-1-infected children. To address their possible patho-physiological significance, we tested the in vitro effects of NO and TNF-alpha in HIV-1 replication. Addition of TNF-alpha and NO donors to mitogen-activated, HIV-1-infected PBMC cultures produced a significant increase in viral replication. Moreover, HIV-1 replication in mitogen-stimulated, PBMC cultures was partially inhibited by iNOS specific inhibitors, and a neutralising, anti-TNF-alpha monoclonal antibody. Our results indicate that TNF-alpha and NO correlated with high viral load in HIV-1-infected children and favoured HIV-1 in vitro replication. These data suggest a detrimental role of NO in HIV-1 infection, and that NOS inhibitors may have some therapeutic benefit in HIV-1-infection.
我们开展了一项横断面研究，以调查44例垂直感染HIV-1的儿童的血浆肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）生成情况，以及它们与免疫状态和病毒复制的关系。作为对照组，我们研究了36名健康、未感染的儿童。采用酶联免疫吸附测定法（ELISA）测定血浆TNF-α和NO水平。使用标准检测方法对病毒载量进行定量。分别通过掺入（3H）-胸腺嘧啶核苷、流式细胞术和p24抗原在体外评估细胞增殖、凋亡和病毒复制。与健康对照组相比，HIV-1感染儿童的血浆TNF-α和NO水平更高。我们发现HIV-1感染儿童的血浆TNF-α和NO水平之间存在非常强的相关性（r = 0.98；p < 0.001）。此外，病毒载量较高（> 4.7 log10）的HIV-1感染儿童的TNF-α和NO水平高于病毒载量低于此阈值的儿童。有趣的是，我们在HIV-1感染儿童的T淋巴细胞中检测到了诱导型一氧化氮合酶（iNOS）mRNA。为了探讨它们可能的病理生理意义，我们测试了NO和TNF-α对HIV-1复制的体外影响。向丝裂原激活的、HIV-1感染的外周血单个核细胞（PBMC）培养物中添加TNF-α和NO供体可使病毒复制显著增加。此外，iNOS特异性抑制剂和一种中和性抗TNF-α单克隆抗体可部分抑制丝裂原刺激的PBMC培养物中的HIV-1复制。我们的结果表明，TNF-α和NO与HIV-1感染儿童的高病毒载量相关，并有利于HIV-1的体外复制。这些数据表明NO在HIV-1感染中起有害作用，并且一氧化氮合酶抑制剂可能对HIV-1感染具有一定的治疗益处。
