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体内注射重组白细胞介素-2可保护小鼠免于败血症死亡。

Administration in vivo of recombinant interleukin 2 protects mice against septic death.

作者信息

Weyand C, Goronzy J, Fathman C G, O'Hanley P

出版信息

J Clin Invest. 1987 Jun;79(6):1756-63. doi: 10.1172/JCI113016.

Abstract

Administration in vivo of recombinant interleukin 2 (rIL-2) to mice induces a polyclonal IgM response. When co-administered with a specific antigen, rIL-2 can enhance concentrations of murine IgM antibodies specific for the antigen by fivefold within 7 d of initial treatment. IgM antibodies that are induced after injection of rIL-2 include antibodies specific for J5, a cell wall core lipopolysaccharide (LPS) antigen that is shared by the different members of the Enterobactericeae family. We report here that mice pretreated with rIL-2 or immunized with J5 antigen 7 d before bacterial challenge were protected from septic death that is caused by intraperitoneal challenges with Escherichia coli. Optimal protection was provided by a combined J5 antigen and rIL-2 treatment. Acquisition of the rIL-2 and J5 antigen-induced protection against lethal bacterial infection coincided temporally with maximal serum IgM titers that also contained IgM antibodies specific for the J5 antigen. In passive immunization experiments, the affinity-purified IgM fraction in sera of rIL-2-treated animals was identified as necessary and sufficient for protection. The IgM-depleted serum had no protective effect. The nonspecific augmentation of host-defense mechanisms without the induction of endotoxin manifestations makes rIL-2 a potential candidate to any alternative LPS-containing vaccines for the prevention of bacterial infections by gram-negative organisms since the core LPS antigen is shared among gram-negative bacteria.

摘要

给小鼠体内注射重组白细胞介素2(rIL-2)可诱导多克隆IgM反应。当与特定抗原共同给药时,rIL-2可在初始治疗7天内将针对该抗原的小鼠IgM抗体浓度提高5倍。注射rIL-2后诱导产生的IgM抗体包括针对J5的抗体,J5是一种细胞壁核心脂多糖(LPS)抗原,为肠杆菌科不同成员所共有。我们在此报告,在细菌攻击前7天用rIL-2预处理或用J5抗原免疫的小鼠,可免受腹腔注射大肠杆菌引起的败血症死亡。联合使用J5抗原和rIL-2治疗可提供最佳保护。获得rIL-2和J5抗原诱导的针对致命细菌感染的保护作用在时间上与最大血清IgM滴度一致,该滴度中也含有针对J5抗原的IgM抗体。在被动免疫实验中,rIL-2处理动物血清中的亲和纯化IgM部分被确定为保护作用所必需且足够。去除IgM的血清没有保护作用。在不诱导内毒素表现的情况下非特异性增强宿主防御机制,使得rIL-2成为任何含LPS替代疫苗的潜在候选者,用于预防革兰氏阴性菌引起的细菌感染,因为核心LPS抗原在革兰氏阴性菌中是共有的。

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