Pollice P F, Hsu J, Hicks D G, Bukata S, Rosier R N, Reynolds P R, Puzas J E, O'Keefe R J
Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
J Orthop Res. 1998 Nov;16(6):697-704. doi: 10.1002/jor.1100160611.
The anti-inflammatory mediator interleukin-10 was investigated as a potential inhibitor of proinflammatory cytokine release in human peripheral blood monocytes activated with titanium particles. It inhibited the secretion of both tumor necrosis factor-alpha and interleukin-6 in a dose-dependent manner, with complete inhibition observed at 2 ng/ml. Co-culture experiments were performed to determine whether this cytokine may have functional importance as an inhibitor of the inflammatory response. When unstimulated lymphocytes and monocytes were co-cultured with titanium-stimulated monocytes, they significantly suppressed the secretion of both interleukin-6 and tumor necrosis factor-alpha. The inhibitory effect of these co-cultured cells could be partially blocked with the addition of an interleukin-10 neutralizing antibody. Interleukin-10 levels were measured in monocyte cultures treated with titanium particles as well as in fresh monocyte cultures treated with conditioned medium from titanium-stimulated monocytes. The latter experiments demonstrated marked stimulation of interleukin-10 secretion in conditioned medium-treated cultures, an effect that was related to the presence of tumor necrosis factor-alpha in the conditioned medium. The addition of titanium to conditioned medium-treated cultures markedly reduced the secretion of interleukin-10, suggesting that the most responsive cells are unstimulated monocytes exposed to agents released from activated monocytes. Altogether, the expression and responsiveness to interleukin-10 suggest a potential role for anti-inflammatory cytokines in regulation of the inflammatory response to wear debris.
抗炎介质白细胞介素-10被作为钛颗粒激活的人外周血单核细胞中促炎细胞因子释放的潜在抑制剂进行研究。它以剂量依赖的方式抑制肿瘤坏死因子-α和白细胞介素-6的分泌，在2 ng/ml时观察到完全抑制。进行共培养实验以确定这种细胞因子作为炎症反应抑制剂是否可能具有功能重要性。当未刺激的淋巴细胞和单核细胞与钛刺激的单核细胞共培养时，它们显著抑制白细胞介素-6和肿瘤坏死因子-α的分泌。这些共培养细胞的抑制作用可通过添加白细胞介素-10中和抗体而部分被阻断。在钛颗粒处理的单核细胞培养物以及用钛刺激的单核细胞的条件培养基处理的新鲜单核细胞培养物中测量白细胞介素-10水平。后一项实验表明，在条件培养基处理的培养物中白细胞介素-10分泌受到显著刺激，这种效应与条件培养基中肿瘤坏死因子-α的存在有关。向条件培养基处理的培养物中添加钛显著降低白细胞介素-10的分泌，表明最敏感的细胞是暴露于活化单核细胞释放的因子的未刺激单核细胞。总之，白细胞介素-10的表达和反应性表明抗炎细胞因子在调节对磨损颗粒的炎症反应中具有潜在作用。
