Trindade M C, Nakashima Y, Lind M, Sun D H, Goodman S B, Maloney W J, Schurman D J, Smith R L
Orthopaedic Research Laboratory, Stanford University School of Medicine, California, USA.
J Orthop Res. 1999 Nov;17(6):797-802. doi: 10.1002/jor.1100170602.
The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocyte-macrophage colony-stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particle-induced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators.
全关节置换术的结果取决于骨-植入物界面处的生物学事件。巨噬细胞吞噬界面处的植入物或磨损碎片，并释放促炎介质，如白细胞介素1和6、肿瘤坏死因子-α和前列腺素E2。这些介质被认为有助于假体周围骨的吸收。先前对从失败的骨科植入物的骨-植入物界面采集的组织进行的研究表明，另外两种细胞因子，即粒细胞-巨噬细胞集落刺激因子和白细胞介素-4可能发挥作用。本研究检测了用聚甲基丙烯酸甲酯颗粒进行体外刺激对原代人单核细胞/巨噬细胞中粒细胞-巨噬细胞集落刺激因子表达的影响，以及白细胞介素-4在调节这种表达中的作用。聚甲基丙烯酸甲酯颗粒在48小时时引起粒细胞-巨噬细胞集落刺激因子的剂量依赖性释放。这种释放伴随着白细胞介素6和1β以及肿瘤坏死因子-α表达的增加。溶酶体酶己糖胺酶的释放也因颗粒而增加。白细胞介素-4在48小时时以剂量依赖性方式抑制粒细胞-巨噬细胞集落刺激因子、白细胞介素-6和肿瘤坏死因子-α的表达。本研究提供的数据证实了以下假设：白细胞介素-4下调颗粒诱导的巨噬细胞活化，这表现为促炎介质释放减少。
