Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine Release In Vitro and In Vivo
Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine Release In Vitro and In Vivo
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DOI：
10.1128/aac.01015-09
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发表时间：
2010-03-01
影响因子：
4.9
通讯作者：
Fox, Stephen D.
中科院分区：
文献类型：
--
作者：
Krakauer, Teresa;Buckley, Marilyn;Fox, Stephen D.
葡萄球菌肠毒素是人体T细胞的有效激活剂，可引起致命的中毒性休克。雷帕霉素是一种免疫抑制剂，检测其抑制葡萄球菌肠毒素B（SE B）体外诱导的人外周血单个核细胞（PBMC）活化和毒素介导的小鼠休克的能力。SEB对PMBC的刺激被雷帕霉素有效地阻断，如通过抑制肿瘤坏死因子α（TNF-α）、白细胞介素1 β（IL-1 β）、IL-6、IL-2、γ干扰素（IFN-γ）、单核细胞趋化蛋白1（MCP-1）、巨噬细胞炎性蛋白1 α（MIP-1 α）、MIP-1 β和T细胞增殖所证明的。在体内，雷帕霉素保护100%的小鼠免于致死性休克，即使在鼻内SEB攻击后24小时给药。与对照组相比，给予雷帕霉素的小鼠鼻内暴露于SEB后，MCP-1和IL-6的血清水平显著降低。此外，雷帕霉素减少了SEB引起的体重减轻和温度波动。
Staphylococcal enterotoxins are potent activators for human T cells and cause lethal toxic shock. Rapamycin, an immunosuppressant, was tested for its ability to inhibit staphylococcal enterotoxin B (SEB)-induced activation of human peripheral blood mononuclear cells (PBMC) in vitro and toxin-mediated shock in mice. Stimulation of PMBC by SEB was effectively blocked by rapamycin as evidenced by the inhibition of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IL-2, gamma interferon (IFN-gamma), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and T-cell proliferation. In vivo, rapamycin protected 100% of mice from lethal shock, even when administered 24 h after intranasal SEB challenge. The serum levels of MCP-1 and IL-6, after intranasal exposure to SEB, were significantly reduced in mice given rapamycin versus controls. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB.