Gongvatana Assawin, Correia Stephen, Dunsiger Shira, Gauthier Lynne, Devlin Kathryn N, Ross Skye, Navia Bradford, Tashima Karen T, DeLaMonte Suzanne, Cohen Ronald A
Department of Psychiatry, University of California, San Diego, USA.
J Neuroimmune Pharmacol. 2014 Dec;9(5):740-50. doi: 10.1007/s11481-014-9567-8. Epub 2014 Oct 2.
HIV-infected individuals frequently exhibit brain dysfunction despite antiretroviral treatment. The neuropathological mechanisms underlying these abnormalities remain unclear, pointing to the importance of identifying biomarkers sensitive to brain dysfunction. We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significantly related to higher volumes of the putamen, thalamus, hippocampus, and WM. Older age was related to lower volumes in most brain regions and higher ventricular volume. Higher IFN-γ, MCP-1, and TNF-α were related to higher volumes of the putamen, pallidum, amygdala, GM, and WM. Higher IL-1β, IL-6, IL-16, IL-18, IP-10, MIP-1β, and SDF-1α were related to lower volumes of the putamen, pallidum, thalamus, hippocampus, amygdala, GM, and WM; and higher ventricular volume. The current findings provide evidence linking smaller brain volumes to HIV disease history, antiretroviral treatment, and advanced age. Cytokine markers, especially IL-6 and IL-16, showed robust association with brain volumes even after accounting for other clinical variables, demonstrating their utility in examining the mechanisms of HIV-associated brain abnormalities.
尽管接受了抗逆转录病毒治疗，但HIV感染者仍经常出现脑功能障碍。这些异常背后的神经病理机制尚不清楚，这凸显了识别对脑功能障碍敏感的生物标志物的重要性。我们使用T1加权磁共振成像（MRI）对74名病情稳定的HIV感染者进行了检查。通过自动分割得出皮质灰质（GM）、白质（WM）、尾状核、壳核、苍白球、丘脑、海马体、杏仁核和脑室的体积。使用多重微珠阵列免疫测定法测量一组血浆细胞因子。在一系列线性回归模型中，使用模型选择算法来选择最能预测每个脑容量测量值的临床和细胞因子标志物组合。更低的CD4最低点、更短的HIV感染持续时间以及抗逆转录病毒治疗与壳核、丘脑、海马体和白质的更大体积显著相关。年龄较大与大多数脑区的较小体积和更大的脑室体积相关。更高的干扰素-γ（IFN-γ）、单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）与壳核、苍白球、杏仁核、灰质和白质的更大体积相关。更高的白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-16（IL-16）、白细胞介素-18（IL-18）、干扰素诱导蛋白10（IP-10）、巨噬细胞炎性蛋白-1β（MIP-1β）和基质细胞衍生因子-1α（SDF-1α）与壳核、苍白球、丘脑、海马体、杏仁核、灰质和白质的较小体积以及更大的脑室体积相关。目前的研究结果提供了证据，将较小的脑体积与HIV疾病史、抗逆转录病毒治疗和高龄联系起来。细胞因子标志物，尤其是IL-6和IL-16，即使在考虑了其他临床变量后，仍与脑体积有很强的关联，证明了它们在研究HIV相关脑异常机制方面的效用。
