SCHAEDLER R W, DUBOS R J
J Exp Med. 1961 Mar 1;113(3):559-70. doi: 10.1084/jem.113.3.559.
Albino mice (Rockefeller NCS strain) raised and maintained free of ordinary bacterial pathogens, as well as of intestinal Escherichia coli and of Proteus bacilli, were found to be highly resistant to the lethal effect of bacterial endotoxins. When newborn mice of this NCS colony were nursed by foster mothers from another colony raised under ordinary conditions (SS colony from which the NCS colony was derived), they acquired the intestinal flora of the latter animals and became susceptible to the lethal effects of endotoxins. NCS adult mice could be rendered susceptible to the lethal effect of endotoxins by vaccination with heat killed Gram-negative bacilli. The susceptibility thus induced exhibited a certain degree of specificity for the bacterial strain used in vaccination. Although untreated NCS mice were resistant to the lethal effect of endotoxins, they proved exquisitively susceptible to the infection-enhancing effect of these materials. For example, 1 microg. or less of endotoxin was found sufficient to help establish a rapidly fatal septicemia with Staphylococcus aureus. Small amounts of endotoxin (1 microg. or less), administered alone, caused a marked but transient loss of weight. Vaccination with heat-killed Gram-negative bacilli or with killed BCG increased the resistance of NCS mice to the infection-enhancing effect of small amounts of endotoxin. This protective effect exhibited a certain degree of specificity for the bacterial strain from which the toxin used in the infection-enhancing test was derived. These various findings can be explained by assuming that the pathological effects of endotoxins involve at least two unrelated mechanisms; (a) a primary toxicity illustrated in this study by the loss of weight and enhancement of infection resulting from the injection of small doses of toxin; (b) an immunological reaction with lethal consequences which became manifest only in animals sensitized to the endotoxin by prior exposure to Gram-negative bacilli.
在无菌条件下饲养和维持的白化小鼠（洛克菲勒NCS品系），即不含普通细菌病原体、肠道大肠杆菌和变形杆菌，被发现对细菌内毒素的致死作用具有高度抗性。当这个NCS群体的新生小鼠由在普通条件下饲养的另一个群体（衍生出NCS群体的SS群体）的代孕母鼠哺育时，它们获得了后者动物的肠道菌群，并变得易受内毒素的致死作用影响。NCS成年小鼠通过接种热灭活革兰氏阴性杆菌可使其对内毒素的致死作用敏感。由此诱导的易感性对用于接种的细菌菌株表现出一定程度的特异性。虽然未处理的NCS小鼠对内毒素的致死作用具有抗性，但它们被证明对这些物质的感染增强作用极为敏感。例如，发现1微克或更少的内毒素足以帮助建立由金黄色葡萄球菌引起的迅速致命的败血症。单独给予少量内毒素（1微克或更少）会导致明显但短暂的体重减轻。接种热灭活革兰氏阴性杆菌或灭活卡介苗可增加NCS小鼠对少量内毒素感染增强作用的抵抗力。这种保护作用对用于感染增强试验的毒素所源自的细菌菌株表现出一定程度的特异性。这些各种发现可以通过假设内毒素的病理作用至少涉及两种不相关的机制来解释：(a) 一种主要毒性，在本研究中表现为注射小剂量毒素导致的体重减轻和感染增强；(b) 一种具有致命后果的免疫反应，只有在先前接触革兰氏阴性杆菌而对内毒素敏感的动物中才会显现出来。
