Proinflammatory Mediators of Toxic Shock and Their Correlation to Lethality
Proinflammatory Mediators of Toxic Shock and Their Correlation to Lethality
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DOI：
10.1155/2010/517594
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发表时间：
2010-01-01
影响因子：
4.6
通讯作者：
Fisher, Diana
中科院分区：
文献类型：
--
作者：
Krakauer, Teresa;Buckley, Marilyn J.;Fisher, Diana
细菌外毒素和内毒素都能刺激促炎介质，但每种毒素在释放导致致死性休克的介质中的作用还不完全清楚。本研究检测了暴露于不同剂量的葡萄球菌肠毒素B（SE B）或脂多糖（LPS）及其组合的小鼠的细胞因子反应和致死率。在体内，单独的SEB诱导中等水平的IL-2和MCP-1，并且即使使用高剂量的SEB（100 μ g/小鼠），所有小鼠也存活。LPS（80 μ g/小鼠）引起48%的致死率并诱导高水平的IL-6和MCP-1。SEB诱导低水平的TNF α、IL-1、IFN γ、MIP-2和LPS，与SEB在这些细胞因子以及IL-6和MCP-1的表达中协同作用。重要的是，SEB和LPS的协同作用导致致死性休克和低温。SEB + LPS组的细胞因子水平与存活状态的ANOVA显示，在8小时测量的非存活者中TNF α、IL-6、MIP-2和MCP-1的水平显著更高。与存活者相比，在21小时时观察到中毒性休克死亡者IFN γ和IL-2水平显著升高。总的来说，SEB和LPS的协同作用导致这些关键细胞因子的水平更高和更长，从而导致中毒性休克。
Bacterial exotoxins and endotoxins both stimulate proinflammatory mediators but the contribution of each individual toxin in the release of mediators causing lethal shock is incompletely understood. This study examines the cytokine response and lethality of mice exposed to varying doses of staphylococcal enterotoxin B (SEB) or lipopolysaccharide (LPS) and their combinations. In vivo, SEB alone induced moderate levels of IL-2 and MCP-1 and all mice survived even with a high dose of SEB (100 mu g/mouse). LPS (80 mu g/mouse) caused 48% lethality and induced high levels of IL-6 and MCP-1. SEB induced low levels of TNF alpha, IL-1, IFN gamma, MIP-2, and LPS synergized with SEB in the expression of these cytokines and that of IL-6 andMCP-1. Importantly, the synergistic action of SEB and LPS resulted in lethal shock and hypothermia. ANOVA of cytokine levels by survival status of SEB-plus-LPS groups revealed significantly higher levels of TNF alpha, IL-6, MIP-2, and MCP-1 in nonsurvivors measured at 8 hours. Significantly higher levels of IFN gamma and IL-2 were observed at 21 hours in nonsurvivors of toxic shock compared to those in survivors. Overall, synergistic action of SEB and LPS resulted in higher and prolonged levels of these key cytokines leading to toxic shock.