抗生素对内毒素活性的增强作用可能会导致安全问题。

Augmenting effect of antibiotics on endotoxin activity may cause a safety problem.

作者信息

Yamamoto Akihiko, Sakai Takeo, Ochiai Masaki, Kamachi Kazunari, Kataoka Michiyo, Toyoizumi Hiromi, Arakawa Yoshichika, Horiuchi Yoshinobu

机构信息

Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

Microbiol Immunol. 2004;48(2):97-102. doi: 10.1111/j.1348-0421.2004.tb03494.x.

DOI:10.1111/j.1348-0421.2004.tb03494.x

PMID:14978334

Abstract

Enhancing/interfering effect of antibiotics on endotoxin was evaluated using the endotoxin test and the cell line assay in 28SC cells that has a responsiveness consistent with that of human peripheral blood. When a total of 21 products of seven different kinds of antibiotics were tested, none showed any significant effect on the endotoxin test at its therapeutic dose. However, aminoglycosides showed a significant augmenting effect on IL-6 induction of endotoxin in 28SC cells. Detailed examination of the augmenting effect was made on spectinomycin in the in vitro cell line assay and also in the lethal endotoxin challenge assay in D -galactosamine-treated mice. Spectinomycin also enhanced the endotoxin lethality in D -galactosamine-treated mice. A kinetic analysis in endotoxin-sensitized 28SC cells revealed that the augmentation takes place as quickly as 10 min after spectinomycin treatment. Accordingly, a special caution concerning the augmenting effect was assumed necessary for the safety control of antibiotic products as well as for selecting antibiotics for the therapeutic use.

摘要

使用内毒素试验和在28SC细胞系中进行的细胞系分析评估抗生素对内毒素的增强/干扰作用，该细胞系的反应性与人类外周血一致。当对7种不同类型的21种抗生素产品进行测试时，在治疗剂量下均未显示出对内毒素试验有任何显著影响。然而，氨基糖苷类抗生素对28SC细胞中内毒素诱导的IL-6有显著增强作用。在体外细胞系分析以及D -半乳糖胺处理的小鼠的致死性内毒素攻击试验中，对壮观霉素的增强作用进行了详细研究。壮观霉素也增强了D -半乳糖胺处理的小鼠的内毒素致死性。对内毒素致敏的28SC细胞的动力学分析表明，壮观霉素处理后10分钟内就会迅速出现增强作用。因此，对于抗生素产品的安全控制以及治疗用抗生素的选择，认为有必要特别注意这种增强作用。