IMMUNOMODULATION OF HIV 1 INFECTED PATIENTS WITH RIL 2

该方案继续了先前的工作，即IL-2可以激发患者的 免疫系统 IL-2是由美国国家生物技术研究所生产的关键产品之一， 缺少CD 4+辅助性T细胞。 然而： a）IL-2在其他情况下是有毒的，特别是肿瘤治疗。 既往毒性最有可能是由于非常高的剂量， 使用，可能是静脉注射途径。 我们使用了较低的剂量 在我们的两个实验中， 研究至今。 B）通过充当T细胞生长因子，IL-2可以活化HIV-1。 等 在临床上已经观察到非常高剂量的IL-2的激活。 IL-2可能触发NK细胞释放TNF，而TNF 激活HIV-1的转录。 然而，我们还没有看到 我们的患者中病毒负荷的显著变化。 仅1/9例患者 bDNA检测显示血浆病毒血症有所上升， 通过在半定量PCR中扩增含gag序列而增加。 尽管如此，我们的患者一直在接受抗病毒治疗 (AZT)，我们将继续监测病毒负荷。 目前提案的基本原理是让患者自行给药 通过皮下途径注射重组IL-2，就像糖尿病患者服用 胰岛素 很明显，这将激活某些方面的 患者的免疫系统，特别是称为“淋巴因子”的细胞， “自然杀手”和“自然杀手”。 现在的目标是记录 增加对HIV-1本身的抵抗力，特别是在 减少感染性病毒的负担，增加病毒水平- 特异性杀伤细胞 有一个有趣的替代方案，即，的 IL-2不会导致病毒负荷的减少，但通过提高CD 4 + T细胞， 细胞计数，将为患者提供抵抗机会性 感染，从而大大提高了生活质量。 的能力 IL-2增加CD 4 + T细胞数量的作用近来已变得明显 几个实验室的研究，包括我们自己的研究。

This protocol continues prior work that IL-2 can energize the patient's immune system. IL-2 is one of the key products that is made by the missing CD4+ helper T cells. However: a) IL-2 has been toxic in other circumstances, especially tumor therapy. Prior toxicities were most likely due to the very high doses that were used, and possibly the intravenous route. We have used lower doses intracutaneously and have encountered minimal toxicities in our two studies to date. b) By acting as a T cell growth factor, IL-2 may activate HIV-1. Such activation has been seen clinically with very high doses of IL-2. Possibly the IL-2 triggers TNF release from NK cells, and the TNF activates transcription of HIV-1. However, we have yet to see significant changes in viral burden in our patients. Only 1/9 patients showed some rise in plasma viremia by bDNA assay, and none showed an increase by amplifying gag containing sequences in semi-quantitative PCR. Nevertheless, our patients have been maintained on anti-viral therapy (AZT), and we will continue to monitor viral burdens. The rationale of the current proposal is to have patients self-administer recombinant IL-2 via the subcutaneous route, much like a diabetic takes insulin. It is already evident that this will activate certain aspects of the patient's immune system, particularly cells called "lymphokine activated killers" and "natural killers". The goal now is to document increased resistance to HIV-1 itself particularly at the level of decreased burdens of infectious virus, and increased levels of virus- specific killer cells. There is an intriguing alternative, i.e., that IL-2 will not lead to a decrease in viral burdens, but by raising CD4+ T cell counts, will provide the patient with resistance to opportunistic infection and hence a greatly improved quality of life. The ability of IL-2 to increase the number of CD4+ T cells has become apparent in recent studies from several Labs, including our own in this protocol.