NORMAL AND PATHOLOGIC MECHANISMS OF INFLAMMATION AND REPAIR

炎症和免疫反应的演变取决于 循环白细胞的募集、迁移和活化 损伤部位或抗原沉积。 长期目标， 实验室专注于表征和调制这些事件。 通过 抑制单核细胞功能并促进IL-1的表达， 受体拮抗剂（IL-1 ra），通过以下途径阻断IL-1的作用： 特异性结合IL-1受体而不引发信号 转导，IL-4可能有助于下调和解决 一种炎症反应。 体外分析IL-4调节 单核细胞表型和功能显示了剂量依赖性诱导， IL-1 ra mRNA在2至4小时内无伴随作用， IL-1 mRNA的表达。 IL-1 ra mRNA的增加不是由于RNA 稳定，但发生在转录水平。 在 LPS、IL-4的存在不仅使IL-1 ra水平升高， 抑制LPS诱导的IL-1 mRNA表达。 外周血单核细胞 从癌症患者，在方案之前和之后立即获得 IL-4免疫治疗组也检测了IL-1 ra基因表达。 IL-4治疗后，患者的单核细胞显示出明显的 IL-1 ra mRNA表达增加。 这种IL-1 ra的诱导作用， 循环单核细胞通过显著增强的血清 IL-4治疗期间IL-1 ra水平（P<0.05），随后 拒绝了。 IL-1 ra通过静息或激活的选择性上调 单核细胞，再加上抑制IL-1的生产，通过激活 单核细胞，正如我们在体外和体内证明的那样，表明 IL-4可能被证明在临床上可用作抗炎剂。

Evolution of inflammatory and immune reactions is dependent upon the recruitment, migration and activation of circulating leukocytes at a site of injury or antigen deposition. Long range goals of this laboratory foucs on characterizing and modulating these events. By suppressing monocyte functions and promoting the expression of an IL-1 receptor antagonist (IL-1ra) that blocks the action f IL-1 by speicifically binding to the IL-1 receptor without initiating signal transduction, IL-4 may contribute to the down-regulation and resolution of an inflammatory response. In vitro analysis of IL-4 regulation of monocyte phenotype and function revealed a dose-dependent induction of IL-1ra mRNA within 2 to 4 hours without a concomitant effect on the expression of IL-1 mRNA. Increased IL-1ra mRNA was not due to RNA stabilization, but occurred at the level of transcription. In the presence of LPS, IL-4 not only augmented IL-1ra levels, but markedly inhibited LPS-induced IL-1 mRNA expression. Peripheral blood monocytes from cancer patients, obtained prior to and immediately after a regimen of IL-4 immunotherapy, were also examined for IL-1ra gene expression. After IL-4 treatment, monocytes from the patients showed a marked increase in the expression of IL-1ra mRNA. This induction of IL-1ra in circulating monocytes was reflected by significantly enhanced serum levels of IL-1ra (P<0.05) during IL-4 therapy which subsequently declined. The selective upregulation of IL-1ra by resting or activated monocytes, coupled with inhibition of IL-1 production by activated monocytes, as we have demonstrated both in vitro and in vivo, suggest that IL-4 may prove clinically useful as an anti-inflammatory agent.