MCP-1 protects mice in lethal endotoxemia
MCP-1 protects mice in lethal endotoxemia
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DOI：
10.1172/jci119475
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发表时间：
1997-06-15
影响因子：
15.9
通讯作者：
Standiford, TJ
中科院分区：
文献类型：
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作者：
Zisman, DA;Kunkel, SL;Standiford, TJ
脓毒症中促炎细胞因子的过度产生可导致休克、多器官功能障碍，甚至死亡。在这项研究中，我们评估了单核细胞趋化蛋白-1（MCP-1）作为内毒素攻击小鼠脓毒症介质的作用。CD-1小鼠腹腔内注射LPS可诱导血浆、肺和肝脏中MCP-1的大量时间依赖性增加。内毒素给药前2 h用兔抗尿MCP-1抗血清被动免疫小鼠，导致LPS诱导的死亡率显著增加，从对照动物的10%增加到抗MCP-1治疗动物的65%。重要的是，给予内毒素攻击的小鼠抗MCP-1抗体导致TNF-α和IL-12峰值水平的增加，并且还导致IL-10血清水平降低的趋势。相反，腹腔注射重组鼠MCP-1可显著保护小鼠免受内毒素诱导的致死性，并导致IL-10水平升高、IL-12水平降低和TNF水平降低的趋势。总之，我们的研究结果表明，MCP-1是一种保护性细胞因子在小鼠内毒素血症中表达，并通过改变平衡，有利于在内毒素攻击的动物中的MCP-1细胞因子的表达。
The overzealous production of proinflammatory cytokines in sepsis can result in shock, multiorgan dysfunction, and even death. In this study, we assessed the role of monocyte chemoattractant protein-1 (MCP-1) as a mediator of sepsis in endotoxin-challenged mice. Intraperitoneal administration of LPS to CD-1 mice induced a substantial time-dependent increase in MCP-1 in plasma, lung, and liver. The passive immunization of mice with rabbit antimurine MCP-1 antiserum 2 h before endotoxin administration resulted in a striking increase in LPS-induced mortality from 10% in control animals to 65% in anti-MCP-1-treated animals. Importantly, the administration of anti-MCP-1 antibodies to endotoxin-challenged mice resulted in increases in peak TNF-alpha and IL-12 levels, and also in a trend toward decreased serum levels of IL-10. Conversely, the administration of recombinant murine MCP-1 intraperitoneally significantly protected mice from endotoxin-induced lethality, and resulted in an increase in IL-10 levels, a decrease in IL-12 levels, and a trend toward decreased levels of TNF. In conclusion, our findings indicate that MCP-1 is a protective cytokine expressed in murine endotoxemia, and does so by shifting the balance in favor of antiinflammatory cytokine expression in endotoxin-challenged animals.