EPIDEMIOLOGY OF CYTOKINE DISREGULATION OF HIV DISEASE

HIV 疾病细胞因子失调的流行病学

• 批准号: 2330422
• 负责人: John L. Fahey
• 金额: $ 26.03万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2330422
• 关键词: HIV infections; cytokine; enzyme linked immunosorbent assay; epidemiology; gene expression; helper T lymphocyte; human subject; interferon gamma; interleukin 10; interleukin 12; interleukin 2; interleukin 4; interleukin 6; male; opportunistic infections; pathologic process; polymerase chain reaction; protein biosynthesis; radioimmunoassay; tissue /cell culture; tumor necrosis factor alpha

DESCRIPTION (adapted from the Abstract): The overall aim of the studies described in this application is to relate alterations in patterns of cytokine expression to the course of HIV infection and disease, by quantifying cytokine production in specific subpopulations of men in the Multicenter AIDS Cohort Study (MACS). In preliminary studies, cytokines that control immune function were found to be altered substantially in HIV infection. The proposed studies are to determine: (1) whether high levels of those cytokines fostering cell-mediated immunity (the TH1 cytokines, interferon-gamma [IFN-gamma] and interleukin-2 [IL-2], as well as IL-12, a cytokine that induces TH1 cells) are associated with relatively stable CD4 T-cell levels and with the absence of opportunistic infection (OI) in HIV infection; (2) whether the predominance of TH2 cytokines (IL-4 and IL-10) is associated with falling CD4 T-cell levels and with the occurrence of OI in HIV infection; (3) whether increases in tumor necrosis factor alpha (TNF-alpha) and IL-6 gene expression/levels are associated with an adverse disease course in the HIV-infected, and whether these cytokines are a better predictor of disease progression than the over-expression of TH-2 cytokines (IL-4 and IL-10); and (4) whether individual and complex changes in cytokine expression have relevance for prognosis (relative hazard) and whether these changes provide prognostic information not available from the measurement of CD4 T-cell number or serum activation markers (e.g., neopterin or beta-2 microglobulin). The subpopulations for study include these cohorts from the MACS: (a) HIV seroconverters; (b) HIV-seropositive men with different rates of decline of CD4 T-cell numbers; (c) HIV-positive men progressing to the acquired immunodeficiency syndrome (AIDS) within three years; (d) long-term HIV-positive survivors with little or no measurable loss of CD4 T-cells; (e) HIV-positive men who have had low CD4 numbers for an extended period of time without the occurrence of OI; and (f) a sample in which selected cytokines can be evaluated for relative hazard of AIDS occurrence. The researchers will measure: (1) serum levels of these cytokines; (2) levels of cytokine gene expression (mRNA) in peripheral blood mononuclear cells (PBMC's) by RNA polymerase chain reaction (PCR); and (3) cytokine production and levels of cytokine mRNA in response to in vitro stimulation of PBMC in the HIV-positive men and in HIV-negative men.

描述（改编自摘要）：研究的总体目标 在本申请中描述的是涉及在本发明的实施例中的图案的改变， 细胞因子表达对HIV感染和疾病过程的影响， 定量研究中特定男性亚群中细胞因子的产生 多中心艾滋病队列研究（MACS）。 在初步研究中， 在HIV中发现控制免疫功能发生了实质性改变 感染 研究的目的是确定：（1）高水平 在那些促进细胞介导的免疫的细胞因子中（TH 1细胞因子， 干扰素-γ [IFN-γ]和白细胞介素-2 [IL-2]，以及IL-12，a 诱导TH 1细胞的细胞因子）与相对稳定的CD 4 T细胞水平和无机会性感染（OI）的HIV 感染;（2）TH 2细胞因子（IL-4和IL-10）的优势是否 与CD 4 T细胞水平下降和OI的发生有关 HIV感染;（3）是否增加肿瘤坏死因子α （TNF-α）和IL-6基因表达/水平与不良反应相关。 HIV感染者的病程，以及这些细胞因子是否是HIV感染者的 比TH-2的过度表达更好地预测疾病进展 细胞因子（IL-4和IL-10）;以及（4）个体和复合体是否改变 在与预后相关细胞因子表达中（相对危险）， 这些变化是否提供了无法从 测量CD 4 T细胞数目或血清活化标志物（例如， 新喋呤或β-2微球蛋白）。 研究的亚群包括 来自MACS的这些队列：（a）HIV血清转换者;（B）HIV血清阳性 CD 4 T细胞数量下降速度不同的男性;（c）艾滋病毒阳性 艾滋病（艾滋病）的发病率。 （d）艾滋病毒抗体呈阳性的长期幸存者， 可测量的CD 4 T细胞损失;（e）患有低CD 4 T细胞的HIV阳性男性 在没有发生OI的情况下，长期使用的数量;以及 (f)其中可以评价所选细胞因子的相对 艾滋病发生的危险。 研究人员将测量：（1）血清水平 （2）这些细胞因子的细胞因子基因表达（mRNA）水平， RNA聚合酶链法检测外周血单个核细胞 反应（PCR）;和（3）细胞因子的产生和细胞因子mRNA的水平， HIV阳性男性和HIV阴性男性对PBMC体外刺激的反应 艾滋病毒阴性男性。