Frank L
J Appl Physiol (1985). 1985 Mar;58(3):819-22. doi: 10.1152/jappl.1985.58.3.819.
To determine if we could reduce endotoxin's potential for toxicity, we produced "endotoxin-tolerant" rats by administering progressively increasing daily doses of endotoxin (10 ng, 100 ng, 1 microgram, 10 micrograms/kg). This dosage regimen produced a high degree of tolerance to the toxic actions of endotoxin: whereas only 3/17 (18%) of control rats survived a normally lethal dose of endotoxin (25 mg/kg), survival for the endotoxin-tolerant rats was 16/16. When endotoxin-tolerant rats received a standard protective dose of 500 micrograms/kg endotoxin just before transfer to 96-98% O2, 19/20 survived the 72-h exposure period vs. 20-30% survival for controls. Thus whereas the endotoxin-tolerant state blocked the tested lethal and toxic effects of endotoxin, it did not nullify the O2 protective action of endotoxin. In addition, endotoxin's stimulatory effects on the lung antioxidant enzymes in the 96-98% O2-exposed rats was also not blocked by the endotoxin-tolerant state. Thus the therapeutic ratio (TR) of endotoxin as an experimental pharmacological treatment against O2-induced lung damage has been markedly enhanced (TR = ratio of dose producing beneficial effects to dose producing toxic effects).
为了确定我们是否能够降低内毒素的潜在毒性，我们通过每天给予递增剂量的内毒素（10纳克、100纳克、1微克、10微克/千克）来培育“内毒素耐受”大鼠。这种给药方案产生了对内毒素毒性作用的高度耐受性：正常致死剂量（25毫克/千克）的内毒素处理后，对照组17只大鼠中只有3只（18%）存活，而内毒素耐受组大鼠全部16只存活。当内毒素耐受大鼠在转移至96 - 98%氧气环境之前接受500微克/千克内毒素的标准保护剂量时，20只中有19只在72小时暴露期内存活，而对照组的存活率为20 - 30%。因此，虽然内毒素耐受状态阻断了内毒素经测试的致死和毒性作用，但并未消除内毒素的氧气保护作用。此外，内毒素耐受状态也未阻断内毒素对暴露于96 - 98%氧气环境中的大鼠肺抗氧化酶的刺激作用。因此，作为针对氧气诱导的肺损伤的实验性药物治疗，内毒素的治疗指数（TR）（TR = 产生有益作用的剂量与产生毒性作用的剂量之比）已显著提高。
