S.aureus induced septic arthritis remains a serious medical concern due to its rapidly progressive disease profile. The multidrug resistant nature of S.aureus demands the development of new strategies for the treatment of S.aureus arthritis. Since monocyte/macrophage population has been recognized as an important axis in joint inflammation and destruction, selective depletion of peripheral blood monocytes might influence the outcome and progression of the disease. Therefore, in this study we have put forward the concept of monocyte depletion by using etoposide, a drug that selectively depletes the monocyte/macrophage population. Mice were inoculated with live S.aureus for the development of septic arthritis. Post S.aureus infection, etoposide was subcutaneously injected. The severity of arthritis was found to be significantly low in the etoposide treated mice throughout the course. Arthritis index, histopathological analysis and TRAP staining images confirmed effectiveness of etoposide treatment in regulating inflammation and bone cartilage destruction. Lower levels of inflammatory cytokines, ROS, MMP-2, RANKL, OPN and plasmin reflected less severe arthritic destruction after etoposide treatment in arthritic mice. The bacterial load was not increased after etoposide treatment. Together, the presented data suggested that monocyte depletion by etoposide might represent an alternative therapeutic strategy for the treatment of S.aureus arthritis.

中文翻译：

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金黄色葡萄球菌感染后依托泊苷介导的外周血单核细胞耗竭通过调节巨噬细胞来源的因子引起炎症破坏而减轻败血性关节炎。

金黄色葡萄球菌引起的败血性关节炎由于其快速进展的疾病状况而仍然是严重的医学问题。金黄色葡萄球菌的多药耐药性要求开发治疗金黄色葡萄球菌关节炎的新策略。由于单核细胞/巨噬细胞群体已被认为是关节炎症和破坏的重要轴，因此外周血单核细胞的选择性消耗可能会影响疾病的结果和进展。因此，在这项研究中，我们提出了通过使用依托泊苷（一种选择性地消耗单核细胞/巨噬细胞群体的药物）来消耗单核细胞的概念。用活的金黄色葡萄球菌接种小鼠以发展化脓性关节炎。金黄色葡萄球菌感染后，依托泊苷皮下注射。在整个过程中，用依托泊苷治疗的小鼠的关节炎严重程度均明显降低。关节炎指数，组织病理学分析和TRAP染色图像证实了依托泊苷治疗在调节炎症和破坏骨软骨方面的有效性。依托泊苷治疗关节炎小鼠后，较低水平的炎性细胞因子，ROS，MMP-2，RANKL，OPN和纤溶酶水平降低了严重的关节炎破坏。依托泊苷治疗后细菌载量没有增加。总之，提出的数据表明依托泊苷消耗单核细胞可能代表了一种治疗金黄色葡萄球菌关节炎的替代治疗策略。组织病理学分析和TRAP染色图像证实了依托泊苷治疗在调节炎症和骨软骨破坏中的有效性。依托泊苷治疗关节炎小鼠后，较低水平的炎性细胞因子，ROS，MMP-2，RANKL，OPN和纤溶酶水平降低了严重的关节炎破坏。依托泊苷治疗后细菌载量没有增加。在一起，提出的数据表明，依托泊苷消耗单核细胞可能代表治疗金黄色葡萄球菌关节炎的替代治疗策略。组织病理学分析和TRAP染色图像证实了依托泊苷治疗在调节炎症和骨软骨破坏中的有效性。依托泊苷治疗关节炎小鼠后，较低水平的炎性细胞因子，ROS，MMP-2，RANKL，OPN和纤溶酶水平降低了严重的关节炎破坏。依托泊苷治疗后细菌载量没有增加。总之，提出的数据表明依托泊苷消耗单核细胞可能代表了一种治疗金黄色葡萄球菌关节炎的替代治疗策略。