Ziegler E J, Douglas H, Braude A I
J Clin Invest. 1973 Dec;52(12):3236-8. doi: 10.1172/JCI107524.
Bacterial lipopolysaccharides from dead bacteria have been blamed for the continuing high mortality from gram-negative infections despite antibiotic treatment. Because animal antiserum against these lipopolysaccharides has been shown to protect against several of the effects of endotoxin, we undertook the development of antiserum in human subjects. 21 men were immunized with a single injection of Salmonclla typhimurium or Escherichia coli 0:111 heat-killed cells and immune serum was collected at 2 wk. Preimmune serum was obtained as a control in all animal experiments. 1 ml antiserum given intravenously protected mice against a lethal intravenous dose of homologous endotoxin (P < 0.005 for both antisera). E. coli antiserum reduced the incidence of positive local Shwartzman reactions with E. coli endotoxin from 100 to 38%; S. typhimurium antiserum reduced the incidence from 92 to 35%. (P < 0.0005 for both antisera). There was no protection against heterologous endotoxin in either animal model. These experiments demonstrate for the first time that human antiserum confers exceedingly potent passive immunity to the effects of endotoxin.
尽管使用了抗生素治疗,但革兰氏阴性菌感染导致的持续高死亡率一直被归咎于死菌的细菌脂多糖。由于动物抗这些脂多糖的抗血清已被证明可抵御内毒素的多种作用,我们着手在人体中研制抗血清。21名男性单次注射鼠伤寒沙门氏菌或大肠杆菌O:111热灭活细胞进行免疫,并在2周时采集免疫血清。在所有动物实验中均获取了免疫前血清作为对照。静脉注射1毫升抗血清可保护小鼠抵御致死剂量的同源内毒素静脉注射(两种抗血清的P均<0.005)。大肠杆菌抗血清使大肠杆菌内毒素局部施瓦茨曼反应阳性的发生率从100%降至38%;鼠伤寒沙门氏菌抗血清使发生率从92%降至35%。(两种抗血清的P均<0.0005)。在两种动物模型中,均未对异源内毒素产生保护作用。这些实验首次证明,人抗血清可赋予对内毒素作用极强的被动免疫力。