BEHAVIORAL DISORDERS AND TNF CHANNELS IN AIDS

临床表现为行为、认知和运动障碍 艾滋病痴呆综合症（ADC） ADC可能是介导的，至少在 部分，由细胞因子肿瘤坏死因子α（TNF-α）和 光毒素（LT）。 TNF和LT是细胞因子分泌的多效细胞因子， 巨噬细胞和淋巴细胞。 TNF和LT具有广泛的 激素和细胞毒性作用，但TNF和 LT是未知的。 我们的实验室最近发现TNF和 LT可以在平面脂质膜中形成离子渗透通道，我们已经 提出，通道的形成可以解释一些生理效应， 肿瘤坏死因子如肿瘤细胞的杀伤和肌肉的去极化 细胞 有几条证据表明TNF参与了 包括艾滋病患者TNF水平升高的事实 患者，TNF可引起恶病质，TNF可增加HIV复制， TNF可以杀死HIV感染的淋巴细胞。 TNF可以增加HIV复制， TNF可以杀死HIV感染的淋巴细胞。 TNF也被发现在 艾滋病患者的CSF及其去活化细胞的能力， 脱髓鞘神经纤维可能导致艾滋病痴呆综合征 （ADC）。 本研究的总体目标是了解 这些渠道在艾滋病的病理生理学，并寻找方法， 改变TNF和LT在AIDS中的破坏作用。 TNF和LT 通道将使用电生理技术表征， 脂质双层和全细胞（膜片钳）。

Behavioral, cognitive, and motor disorders are clinical manifestations of AIDs Dementia Complex (ADC). ADC is likely mediated, at least in part, by the cytokines tumor necrosis factor alpha (TNF-alpha) and lymphotoxin (LT). TNF and LT are pleiotropic cytokines secreted by macrophages and lymphocytes. TNF and LT possess a broad range of hormonal and cytotoxic actions, but the mechanism of action of TNF and LT is unknown. Our laboratory has made the recent discovery that TNF and LT can form ion-permeable channels in planar lipid membranes, and we have proposed that channel formation may explain some physiologic effects of TNF such as the killing of tumor cells and the depolarization of muscle cells. Several lines of evidence implicate TNF in the pathophysiology of AIDS including the facts that TNF levels are elevated in AIDS patients, TNF can cause cachexia, TNF can increase HIV replication, and TNF can kill HIV-infected lymphocytes. TNF can increase HIV replication, and TNF can kill HIV-infected lymphocytes. TNF has also been found in the CSF of AIDS patients and its ability to depolarize cells and demyelinate nerve fibers may contribute to the dementia complex of AIDS (ADC). The broad goal of this research is to understand the role of these channels in the pathophysiology of AIDS and to search for ways to modify the destructive actions of TNF and LT in AIDS. TNF and LT channels will be characterized using electrophysiologic techniques in lipid bilayer and whole cells (patch clamp).