EXPRESSION OF LPS-INDUCIBLE CYTOKINES BY HUMAN MONOCYTES

细胞因子作为治疗剂的使用因以下事实而复杂化 他们不会单独行动。细胞因子网络的解剖 揭示了大多数细胞因子都受到高度调控，以应对 其他细胞因子水平。目前的焦点是内毒素介导的 人单核细胞的反应及其对刺激的调节作用 单核细胞分化，特别是干扰素-γ和 菌落刺激因子。这项工作揭示了诱导 单核细胞产生的关键生物活性细胞因子可高度受 这些外源性细胞因子的存在。对和的依赖 启动的效果因所检测的单体不同而不同。例如, IL-12只有在干扰素-伽马刺激后才被诱导，而干扰素-α则是 在用干扰素-γ或GM-CSF预注后诱导。当前 研究旨在确定关键的细胞内因子， 消除这些影响。这将为以下方面提供有用的信息 了解细胞因子在体内是如何相互作用的，这应该有助于预测 体内对外源细胞因子的反应。 这项研究揭示了关于特定能力的关键信息 细胞因子调节其他细胞因子的表达并影响 单核细胞的分化。这些细胞因子中的许多都处于低潮 在分区中进行审查。我们没有足够的信息来说明 这些细胞因子在孤立的情况下起作用，这会导致 关于它们在体内如何发挥作用的预测。此外，这项工作 需要持续了解评估存在的方法和 多种细胞因子的活性。脓毒症患者细胞因子水平的变化 在患者监测中变得很重要，可能还在预测 结果。我们实验室最近的工作是解决 树突状细胞表达IL-12。目前，CBER正在收到大量IND 建议在各种疫苗中使用树突状细胞。研究 树突状细胞中IL-12的表达将提供一个很好的标记物 疫苗产品中这些细胞的功能和活性。

The use of cytokines as therapeutic agents is complicated by the fact that they do not act in isolation. The dissection of cytokine networks reveals that most cytokines are highly regulated in response to the levels of other cytokines. The current focus is on LPS-mediated responses of human monocytes and their modulation by stimuli that affect monocyte differentiation, particularly interferon-gamma and colony-stimulating factors. This work has revealed that the induction of critical bio-active cytokines from monocytes can be highly influenced by the presence of these exogenous cytokines. The dependence upon, and effects of, priming differ with each monokine examined. For example, IL-12 is induced only after IFN-gamma priming, while IFN-alpha is induced following priming with either IFN-gamma or GM-CSF. Current studies are designed to identify critical intracellular factors that nediate these effects. This should provide useful information for understanding how cytokines interact in vivo, which should help predict the outome of in vivo responses to exogenous cytokines. This research reveals critical information about the capacity of specific cytokines to regulate the expression of other cytokines and affect differentiation of monocytes. Many of these cytokines are under current review in the division. We cannot have enough information about how these cytokines work in isolated circumstances, which gives rise to predictions about how they may function in vivo. In addition, this work requires continuing knowledge of methods for assessing the presence and activity of a variety of cytokines. Cytokine levels in sepsis patients have become important in patient monitoring and possibly in predicting outcome. Recent work in our laboratory is addressing the expression of IL-12 in dendritic cells. Currently, CBER is receiving numerous INDs proposing the use of dendritic cells in a variety of vaccines. Studies of IL-12 expression in dendritic cells will provide an excellent marker for the function and activity of these cells in vaccine products.