NORMAL AND PATHOLOGIC MECHANISMS OF INFLAMMATION AND REPAIR

炎症和免疫反应的演变取决于 循环中白细胞的募集、迁移和激活 损伤或抗原沉积的部位。这方面的长期目标 实验室致力于表征和调节这些事件。通过 抑制单核细胞功能，促进IL-1的表达 受体拮抗剂(IL-1ra)，通过以下途径阻断IL-1的作用 与IL-1受体特异性结合而不启动信号 转导、IL-4可能参与下调和分解 是一种炎症反应。IL-4对血管内皮细胞生长调节的体外分析 单核细胞表型和功能显示剂量依赖性诱导 IL-1ra信使核糖核酸在2~4小时内表达，对细胞无明显影响 IL-1mRNA的表达。IL-1ra mRNA的增加不是由于RNA引起的 稳定，但发生在转录水平。在 内毒素、IL-4的存在不仅使IL-1ra水平升高，而且显著 抑制脂多糖诱导的IL-1mRNA表达。外周血单核细胞 来自癌症患者，在服药前和服药后立即获得 IL-4免疫治疗组，检测IL-1ra基因表达。 在IL-4治疗后，患者的单核细胞表现出明显的 IL-1ra mRNA表达增加。IL-1ra在BALB细胞中的诱导 循环单核细胞被显著升高的血清所反映 IL-4治疗期间IL-1ra(P&lt；0.05)水平的变化 谢绝了。静息或激活对IL-1ra的选择性上调 单核细胞，再加上激活后抑制IL-1的产生 单核细胞，正如我们在体外和体内所证明的那样，表明 IL-4可能被证明是一种临床上有用的抗炎剂。

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.