MODULATION OF HIV-1 REPLICATION BY CYTOKINES AND SOLUBLE CYTOKINE RECEPTORS

细胞因子是细胞衍生的蛋白质，在体内起激素的作用 免疫系统，影响细胞的生长和分化。他们的 对人类细胞的影响使细胞因子能够调节HIV-1的复制。 我们正在确定各种细胞因子对艾滋病毒复制的影响 淋巴细胞和单核细胞，参与免疫反应的细胞，以及 容易感染艾滋病毒的。因为有能力控制 细胞因子介导的HIV复制修饰很重要 在治疗方面，我们正在研究天然拮抗剂的能力 控制细胞因子对HIV复制的调控。我们已经证明了 HIV在人类细胞中的复制可以由细胞因子TNF-a， 而这种诱导可以通过使用可溶性的肿瘤坏死因子受体来逆转。 我们现在发现，硒可以调节肿瘤坏死因子对艾滋病病毒复制的影响 慢性感染MO和T细胞，但仅限于急性感染MO。 我们还发现，干扰素-a物种/成分在它们的能力上存在差异。 抑制艾滋病毒复制，这可能有助于选择毒性较低的 可在体内使用的干扰素-α。 我的实验室正在进行的工作是为了了解 涉及细胞因子和/或其可溶性受体的现有网络 在体外和体内发挥作用。对这一机制的理解可以使 以获取更详细和科学的方法来审查新的 产品，包括细胞因子和可溶性细胞因子受体，建议用于 作为体内细胞因子活性拮抗剂的治疗应用。因为我的 实验室表明，细胞因子和细胞因子之间存在微妙的平衡。 它们的拮抗剂，使细胞因子的增强和抑制 生物活动可以通过改变它们的浓度来产生，它释放 对提议的治疗用途存在的复杂性的新认识 这些特工的名字。我们的发现也可能有助于确定 接受细胞因子或药物治疗的患者需要监测的参数 可溶性细胞因子受体。

Cytokines are cell-derived proteins that function as hormones in the immune system and affect cellular growth and differentiation. Their effects on human cells enable cytokines to modulate replication of HIV-1. We are determining the effects of various cytokines on HIV replication in lymphocytes and monocytes, cells involved in the immune response and also susceptible to infection with HIV. Since the ability to control cytokine-mediated modification of HIV replication is important therapeutically, we are studying the ability of natural antagonists to control modulation of HIV replication by cytokines. We have shown that replication of HIV in human cells can be induced by the cytokine, TNF-a, and that this induction can be reversed by using soluble TNF receptors. We now find that selenium can modulate TNF effects on HIV replication in chronically infected MO and T cells, but only on acute infection of MO. We also find that IFN-a species/components vary in their ability to inhibit HIV replication, which may facilitate selection of a less toxic IFN-a that can be used in vivo. The work ongoing in my laboratory is directed at understanding how existing networks involving cytokines and/or their soluble receptors function in vitro and in vivo. An understanding of this mechanism allows for a more detailed and scientific approach to the review of new products, both cytokines and soluble cytokine receptors, proposed for therapeutic use as antagonists to cytokine activity in vivo. Since my laboratory has shown that a delicate balance exists between cytokines and their antagonists, such that both enhancement and inhibition of cytokine biologic activity can result by altering their concentrations, it sheds new light on the complexities that exist for the proposed therapeutic use of these agents. Our findings may also assist in determining what parameters to monitor in patients that are receiving either cytokines or soluble cytokine receptors.