Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis.

Circulatory shock Pub Date : 1994-02-01
R Saladino, C Garcia, C Thompson, B Hammer, J Parsonnet, T Novitsky, G Siber, G Fleisher
{"title":"Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis.","authors":"R Saladino,&nbsp;C Garcia,&nbsp;C Thompson,&nbsp;B Hammer,&nbsp;J Parsonnet,&nbsp;T Novitsky,&nbsp;G Siber,&nbsp;G Fleisher","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":10280,"journal":{"name":"Circulatory shock","volume":"42 2","pages":"104-10"},"PeriodicalIF":0.0000,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulatory shock","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)

重组内毒素中和蛋白对家兔大肠杆菌败血症的治疗效果。
革兰氏阴性细菌性败血症与内毒素血症和高死亡率有关。在之前的研究中,我们证明了从多足鲎变形细胞中分离的抗脂多糖因子,以及该蛋白的重组版本,称为内毒素中和蛋白(ENP),在纯化脂多糖刺激的兔子中具有治疗作用。为了评估ENP治疗活细菌感染的益处,我们建立了一种大肠杆菌腹膜炎和菌血症的兔子模型,尽管庆大霉素治疗,但死亡率很高。24对新西兰大白兔腹腔注射含5%猪黏液的大肠杆菌O18ac K1(每剂量平均细菌数= 2.5 × 10(8))。小鼠在大肠杆菌攻毒后1小时静脉注射庆大霉素(2.5 mg/kg)和ENP (5 mg/kg)或生理盐水。所有家兔在攻毒后1小时呈菌血症(几何平均值4.1 +/- 1.2 × 10(4) cfu/mL)。enp处理动物的峰值几何平均血清内毒素(2.62 v 10.54 EU/mL, P = 0.013)和肿瘤坏死因子(TNF) (2540 v 6438 TNF单位/mL, P = 0.046)浓度低于对照动物。24只接受ENP治疗的动物中有7只存活了24小时,而24只对照组中有4只存活了24小时(Kaplan-Meier分析,P = .19)。然而,在庆大霉素治疗消除菌血症的13只配对动物亚组中,13只接受enp治疗的动物中有5只存活了24小时,而13只对照组中有1只存活了24小时(Kaplan-Meier分析,P = 0.032)。(摘要删节250字)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信