REGULATION OF INTERLEUKIN-6 (IL-6)

白细胞介素-6（IL-6）是一种具有多种功能的炎性细胞因子 包括体液和细胞免疫应答的调节， 诱导血小板生成。 这种细胞因子可以具有治疗性和 病理效应取决于体内发现的水平;异常高 IL-6的水平是有害的，并有助于疾病的发展， 适当的免疫功能需要生理水平的IL-6 和血小板生成。 我们工作的目标是阐明 从而在体内控制IL-6水平。 我们培育了一种 用于此目的的临床前模型。 实验系统包括 诱导炎症反应，伴随着长期的 高水平的IL-6。 我们的数据显示，为了使炎症 化合物诱导PGE 2介导的IL-6合成，它必须诱导表达 环氧合酶-2是一种可诱导的前列腺素合成酶同工酶。 目前，IL-6正在开发用于三种临床用途： 作为刺激血小板的治疗剂给药 （B）临床方案， 降低IL-6活性的方法正在被开发作为一种手段，以阻止其 作为肿瘤促进剂的作用;和（c）IL-6作为临床诊断剂， 多发性骨髓瘤和类风湿性关节炎等疾病的标志物。 我们的研究旨在阐明 控制IL-6的合成和周转。 这些研究涉及验证 用于测量生物流体中IL-6水平的测定。 我们研究的关键 是使用一个临床前模型，使我们能够衡量控制 IL-6水平和IL-6诱导体内致瘤性的机制。 我们 研究计划有助于CBER科学家监管的能力 IL-6作为治疗剂，因为它探索了两种体外方法， 检测体液和临床前模型中的IL-6， 体内IL-6调节。

Interleukin-6 (IL-6) is an inflammatory cytokine with diverse functions including regulation of the humoral and cellular immune response and induction of thrombopoiesis. This cytokine can have both therapeutic and pathologic effects depending on the levels found in vivo; abnormally high levels of IL-6 are deleterious and contribute to disease development while physiological levels of IL-6 are required for appropriate immune function and thrombopoiesis. The goal of our work is to elucidate the mechanisms whereby IL-6 levels are controlled in vivo. We have developed a murine pre-clinical model for this purpose. The experimental system involves induction of an inflammatory response that is accompanied by prolonged high levels of IL-6. Our data show that in order for an inflammatory compound to induce PGE2-mediated IL-6 synthesis, it must induce expression of cyclooxygenase-2, which is an inducible prostaglandin synthase isozyme. Currently, IL-6 is under development for three clinical uses: (a) IL-6 is being administered as a therapeutic agent for stimulation of platelet production following chemotherapy; (b) Clinical protocols designed to diminish the activity of IL-6 are being developed as a means to block its action as a tumor promoter; and (c) IL-6 serves as a clinical diagnostic marker for diseases such as multiple myeloma and rheumatoid arthritis. Our research is designed to elucidate the biological mechanisms that control IL-6 synthesis and turnover. These studies involve validation of assays to measure IL-6 levels in biological fluids. Key to our research is the use of a pre-clinical model which allows us to measure control of IL-6 levels and mechanisms of IL-6-induced tumorigenicity in vivo. Our research program contributes to the ability of CBER scientists to regulate IL-6 as a therapeutic agent in that it explores both in vitro methods for testing IL-6 in body fluids and pre-clinical models that help to predict IL-6 regulation in vivo.