Beutler B, Milsark I W, Cerami A C
Science. 1985 Aug 30;229(4716):869-71. doi: 10.1126/science.3895437.
A highly specific polyclonal rabbit antiserum directed against murine cachectin/tumor necrosis factor (TNF) was prepared. When BALB/c mice were passively immunized with the antiserum or with purified immune globulin, they were protected against the lethal effect of the endotoxin lipopolysaccharide produced by Escherichia coli. The prophylactic effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin. Antiserum to cachectin/TNF did not mitigate the febrile response of endotoxin-treated animals, and very high doses of endotoxin could overcome the protective effect. The median lethal dose of endotoxin in mice pretreated with 50 microliters of the specific antiserum was approximately 2.5 times greater the median lethal dose for controls given nonimmune serum. The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin.
制备了一种针对小鼠恶病质素/肿瘤坏死因子(TNF)的高度特异性多克隆兔抗血清。当用该抗血清或纯化的免疫球蛋白对BALB/c小鼠进行被动免疫时,它们能免受大肠杆菌产生的内毒素脂多糖的致死作用。这种预防作用是剂量依赖性的,并且在注射内毒素之前给予抗血清时最为有效。恶病质素/TNF抗血清并不能减轻内毒素处理动物的发热反应,而且非常高剂量的内毒素可以克服这种保护作用。用50微升特异性抗血清预处理的小鼠中,内毒素的半数致死剂量大约是给予非免疫血清的对照组的2.5倍。数据表明恶病质素/TNF是内毒素致死作用的主要介质之一。