Acute inflammatory response to endotoxin in mice and humans
Acute inflammatory response to endotoxin in mice and humans
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DOI：
10.1128/cdli.12.1.60-67.2005
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Remick, D
中科院分区：
文献类型：
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作者：
Copeland, S;Warren, HS;Remick, D
内毒素注射剂已被广泛用于急性炎症反应的研究。在这项研究中，我们直接比较了小鼠和人类对内毒素的炎症反应。大肠杆菌O113型内毒素是在相同的条件下制备的，经验证具有同等的生物学效力，并用于小鼠和人类。注射后2小时，要使血浆中的白介素6(IL-6)浓度接近1000pg/ml，所需的内毒素剂量为人体体重的2 ng/kg和小鼠的500 ng/kg。健康成年志愿者静脉注射内毒素，雄性C57BL/6小鼠(n=4~12)腹腔注射内毒素。测定生理、血液学和细胞因子反应。内毒素在人体内引起快速的生理反应(发烧、心动过速和轻微的低血压)，但在小鼠身上不能。小鼠和人均出现淋巴细胞减少，4h达最低点，2 4h恢复正常，血浆中肿瘤坏死因子(TNF)和IL-6水平在2h达到峰值，4~6h恢复到基线水平，IL-1受体拮抗剂RA和TNF可溶性受体I在小鼠和人中均上调，但在人中上调幅度更大。小鼠产生更高水平的CXC趋化因子，小鼠和人类在2小时出现高峰。这些研究表明，尽管存在差异，小鼠需要更高的内毒素刺激，但小鼠和人类对内毒素的炎症反应有几个相似之处。
Endotoxin injection has been widely used to study the acute inflammatory response. In this study, we directly compared the inflammatory responses to endotoxin in mice and humans. Escherichia coli type O113 endotoxin was prepared under identical conditions, verified to be of equal biological potency, and used for both mice and humans. The dose of endotoxin needed to induce an interleukin-6 (IL-6) concentration in plasma of similar to1,000 pg/ml 2 h after injection was 2 ng/kg of body weight in humans and 500 ng/kg in mice. Healthy adult volunteers were injected intravenously with endotoxin, and male C57BL/6 mice (n = 4 to 12) were injected intraperitoneally with endotoxin. Physiological, hematological, and cytokine responses were determined. Endotoxin induced a rapid physiological response in humans (fever, tachycardia, and slight hypotension) but not in mice. Both mice and humans exhibited lymphopenia with a nadir at 4 h and recovery by 24 h. The levels of tumor necrosis factor (TNF) and IL-6 in plasma peaked at 2 It and returned to baseline levels by 4 to 6 h. IL-1 receptor antagonist RA and TNF soluble receptor I were upregulated in both mice and humans but were upregulated more strongly in humans. Mice produced greater levels of CXC chemokines, and both mice and humans exhibited peak production at 2 h. These studies demonstrate that although differences exist and a higher endotoxin challenge is necessary in mice, there are several similarities in the inflammatory response to endotoxin in mice and humans.