EPIDEMIOLOGY OF CYTOKINE DISREGULATION OF HIV DISEASE

说明(改编自摘要)：研究的总体目标 在本申请中描述的是涉及以下图案的改变 细胞因子在HIV感染和疾病过程中的表达 量化男性特定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，细胞因子 控制免疫功能在HIV中被发现有很大的改变 感染。拟议的研究将确定：(1)高水平 在那些促进细胞免疫的细胞因子中(TH1细胞因子， 干扰素-γ[干扰素-γ]和白细胞介素2[IL-2]以及IL-12，a 诱导TH1细胞的细胞因子)与相对稳定的CD4有关 T细胞水平和HIV中无机会性感染(OI) 感染；(2)TH2类细胞因子(IL-4和IL-10)是否占优势 与CD4T细胞水平下降和OI的发生有关 在HIV感染中；(3)肿瘤坏死因子α是否增加 (肿瘤坏死因子-α)和白介素6基因表达/水平与不利的 HIV感染者的病程，以及这些细胞因子是否是 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)是否个别和复杂的变化 细胞因子的表达与预后(相对风险)和 这些变化是否提供了无法从 测量CD4T细胞数量或血清激活标志物(例如， 新喋呤或β-2微球蛋白)。研究的亚群包括 这些来自互委会的队列：(A)艾滋病毒血清转换者；(B)艾滋病毒血清阳性 男性CD4T细胞数量有不同程度的下降；(C)艾滋病毒阳性 男性体内进展为获得性免疫缺陷综合征(艾滋病) 三年；(D)艾滋病毒长期阳性幸存者，几乎没有或几乎没有 可测量的CD4T细胞损失；(E)CD4值低的艾滋病毒阳性男子 在较长一段时间内没有发生OI的数字；以及 (F)可对选定的细胞因子进行相对评价的样本 艾滋病发生的危害性。研究人员将测量：(1)血清水平 这些细胞因子；(2)细胞因子基因表达水平 用RNA聚合酶链法检测外周血单个核细胞 (3)细胞因子的产生和细胞因子的mRNA水平。 HIV阳性男性和女性对PBMC体外刺激的反应 艾滋病毒阴性的男人。

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.