Westmoreland S V, Kolson D, González-Scarano F
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-6146, USA.
J Neurovirol. 1996 Apr;2(2):118-26. doi: 10.3109/13550289609146545.
A significant proportion of HIV-1 infected individuals develop a symptom complex consisting of dementia and motor deficits termed HIV Dementia (HIVD) or the AIDS Dementia complex (ADC). The pathophysiology of this neurologic complication is unclear, but neuronal injury and death may occur as a direct result of the release of cytokines from HIV-1 infected microglial cells (Everall et al, 1991). To evaluate the utility of a human neuronal cell line, NT2N, for studies of HIV-related neuronal cytotoxicity, we studied cellular viability after exposure to HIV-1 gp120, tumor necrosis factor alpha (TFN alpha), platelet activating factor (PAF), interleukin 1 beta (IL-1 beta), and interferon gamma (IFN gamma), all of which have been implicated in previous publications as having a role in HIVD (Brenneman et al, 1988; Dreyer et al, 1990; Merrill et al, 1992; Gelbard et al, 1993). Neither gp 120 nor the cytokines IL-1 beta and IFN gamma resulted in significant NT2N cell death. However, TNF alpha and PAF were highly neurotoxic in this assay. Pentoxifylline, which inhibits the effects of TNF alpha, had a significant protective effect. This system provides an excellent substrate for the evaluation of neurotoxicity and for the development of pharmacologic agents that may be useful in HIV dementia.
相当一部分感染了HIV-1的个体出现了一种症状复合体，包括痴呆和运动功能障碍，称为HIV痴呆（HIVD）或艾滋病痴呆综合征（ADC）。这种神经并发症的病理生理学尚不清楚，但神经元损伤和死亡可能是HIV-1感染的小胶质细胞释放细胞因子的直接结果（埃弗拉尔等人，1991年）。为了评估人神经元细胞系NT2N在研究HIV相关神经元细胞毒性中的作用，我们研究了NT2N细胞在暴露于HIV-1 gp120、肿瘤坏死因子α（TFNα）、血小板活化因子（PAF）、白细胞介素1β（IL-1β）和干扰素γ（IFNγ）后的细胞活力，所有这些在以前的出版物中都被认为与HIVD有关（布伦内曼等人，1988年；德雷尔等人，1990年；梅里尔等人，1992年；盖尔巴德等人，1993年）。gp120以及细胞因子IL-1β和IFNγ均未导致NT2N细胞显著死亡。然而，在该试验中，TNFα和PAF具有高度神经毒性。抑制TNFα作用的己酮可可碱具有显著的保护作用。该系统为评估神经毒性和开发可能对HIV痴呆有用的药物提供了一个极好的底物。
