CYTOKINE RELEASE FROM MICROGLIA - DIFFERENTIAL INHIBITION BY PENTOXIFYLLINE AND DEXAMETHASONE

CYTOKINE RELEASE FROM MICROGLIA - DIFFERENTIAL INHIBITION BY PENTOXIFYLLINE AND DEXAMETHASONE
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DOI:
10.1093/infdis/166.4.847
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发表时间:
1992-10-01
影响因子:
6.4
通讯作者:
PETERSON, PK
PETERSON, PK
中科院分区:
医学2区
文献类型:
--
作者:
CHAO, CC;HU, SX;PETERSON, PK

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细胞因子与革兰氏阴性细菌性脑膜炎的发病机制有关。采用生物测定法探讨了戊茶碱和地塞米松对原代小鼠小胶质细胞培养物中肿瘤坏死因子(TNF)、白细胞介素(IL)-1和IL-6释放的影响。当与脂多糖同时加入时,喷替茶碱阻断TNF和IL-1的释放,但不阻断IL-6的释放,而地塞米松抑制TNF和IL-6的释放。小胶质细胞暴露于脂多糖2小时后,喷替福林而不是地塞米松仍然抑制TNF的释放。TNF的释放增强了20倍,由小胶质细胞与干扰素-γ的启动,只有喷替福林阻断干扰素-γ对TNF释放的启动作用。这些结果表明,喷替福林和地塞米松差异调节小胶质细胞培养物中细胞因子的释放,并提供潜在的洞察他们在治疗革兰氏阴性细菌性脑膜炎的作用。
Cytokines have been implicated in the pathogenesis of gram-negative bacterial meningitis. The effects of pentoxifylline and dexamethasone on the release of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 from primary murine microglial cell cultures were explored using bioassays. When added concomitantly with lipopolysaccharide, pentoxifylline blocked the release of TNF and IL-1 but not IL-6, while dexamethasone inhibited the release of TNF and IL-6. After a 2-h exposure of microglia to lipopolysaccharide, pentoxifylline but not dexamethasone still inhibited the release of TNF. Release of TNF was enhanced 20-fold by priming of the microglia with interferon-gamma; only pentoxifylline blocked the priming effect of interferon-gamma on TNF release. These results demonstrate that pentoxifylline and dexamethasone differentially regulate the release of cytokines in microglial cell cultures and provide potential insight into their role in the treatment of gram-negative bacterial meningitis.