Microglial inflammation is the hallmark of S. aureus induced brain abscesses. Conventional antibiotic therapy could not regulate inflammation and the use of steroids in CNS infection remained controversial. To address this issue the effect of dexamethasone along with ciprofloxacin on microglial inflammation has been attempted both in glucocorticoid receptor (GR) opened and blocked condition. We have investigated the effects of ciprofloxacin (0.24 μg/ml, pre-treatment) and dexamethasone (150 nM, pre-treatment) in combination with murine microglia infected with S. aureus for 30, 60 and 90 min by either keeping GR opened or blocked with GR antagonist RU486. Alterations in cellular motility, intracellular killing assay, free radical production, antioxidant enzyme activities, corticosterone, and cytokine levels were determined. The expressions of TLR-2, GR, and other inflammatory markers were determined in terms of this combinatorial treatment. Combination treatment significantly (p < 0.05) reduced the bacterial burden of microglia only when GR remained open and effectively suppressed S. aureus induced oxidative stress by augmenting SOD and catalase enzyme activity and suppressing other pro-inflammatory markers at 90 min. Arginase activity, a critical determinant of microglial polarization was found to be higher after treatment at 60 and 90 min. This situation was reversed when this combination treatment was applied by keeping GR blocked using GR antagonist RU486. Therefore, it can be concluded that combination treatment of ciprofloxacin and dexamethasone could regulate S. aureus induced microglial activation, in the presence of functional GR via utilizing glucocorticoid (GC)-GR pathway and ultimately confers protection to the host from brain inflammation.

中文翻译：

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地塞米松和环丙沙星通过糖皮质激素 (GC)-GC 受体介导的途径调节金黄色葡萄球菌诱导的小胶质细胞炎症。

小胶质细胞炎症是金黄色葡萄球菌引起的脑脓肿的标志。传统的抗生素治疗无法调节炎症，在中枢神经系统感染中使用类固醇仍然存在争议。为了解决这个问题，地塞米松与环丙沙星对小胶质细胞炎症的影响已在糖皮质激素受体 (GR) 开放和阻断状态下进行了尝试。我们研究了环丙沙星（0.24 μg/ml，预处理）和地塞米松（150 nM，预处理）与感染金黄色葡萄球菌的鼠小胶质细胞 30、60 和 90 分钟的效果，方法是保持 GR 打开或用 GR 拮抗剂 RU486 阻断。测定了细胞运动、细胞内杀伤试验、自由基产生、抗氧化酶活性、皮质酮和细胞因子水平的变化。TLR-2的表达，根据这种组合治疗确定了 GR 和其他炎症标志物。只有当 GR 保持开放并通过增加 SOD 和过氧化氢酶活性并在 90 分钟时抑制其他促炎标志物来有效抑制金黄色葡萄球菌诱导的氧化应激时，联合治疗才能显着降低小胶质细胞的细菌负荷 (p < 0.05)。精氨酸酶活性是小胶质细胞极化的一个关键决定因素，在 60 和 90 分钟处理后发现更高。当通过使用 GR 拮抗剂 RU486 保持 GR 阻断来应用这种联合治疗时，这种情况得到了逆转。因此，可以得出结论，环丙沙星和地塞米松联合治疗可以调节金黄色葡萄球菌诱导的小胶质细胞活化，