Soluble TNFR II/IgG1 Fc fusion protein treatment in the LPS-mediated septic shock of rats

被引：14

作者：

Guo, Zhuying ^{[1
]}

Wang, Shiting ^{[1
]}

Hao, Qiang ^{[1
]}

Xu, Manghua ^{[1
]}

Xu, Zhimei ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Affiliated Hosp 3, Expt Ctr, Shanghai 201900, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2009年 / 63卷 / 07期

关键词：

Lipopolysaccharide; Septic shock; Tumor necrosis factor-alpha; Soluble tumor necrosis factor-alpha receptor/IgG1 Fc fusion protein; TUMOR-NECROSIS-FACTOR; ENDOTOXIN-INDUCED UVEITIS; INDUCED LIVER-INJURY; FACTOR-ALPHA; CROHNS-DISEASE; IFN-GAMMA; IN-VIVO; EXPRESSION; ETANERCEPT; INFLIXIMAB;

D O I：

10.1016/j.biopha.2008.08.012

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Tumor necrosis factor-alpha (TNF-alpha) is thought to play a major role in systemic inflammation associated with sepsis. A potent TNF antagonist, a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (sTNFR II/IgG1 Fc fusion protein, sTNFR:Fc), has been shown to provide rapid and sustained improvement in local inflammation diseases by binding TNF-alpha and preventing its proinflammatory activities. To explore the potential therapeutic efficacy for septic shock of sTNFR:Fc, we investigate the effect of this molecule on the survival rate, blood pressure, serum TNF-alpha bioactivity as well as the expression of TNF-alpha at mRNA level in the liver in a LPS-induced rat septic shock model. Blood pressure of the rats was monitored by multi-channel creature signal analysis system. Serum TNF-alpha level and bioactivity was assessed using an enzyme-linked immunoassay and a L929 cytotoxicity assay, respectively. The expression of TNF-alpha mRNA in liver was examined by semi-quantitativc RT-PCR. sTNFR:Fc administered to rats 24 h before LPS challenge ablated the rise in serum TNF-alpha bioactivity that occurs in response to LPS and protected against hypotension and death. These results indicate that TNF-alpha is a mediator of fatal septic shock, and suggest that sTNFR:Fc offer a potential therapy of systemic infection. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：537 / 542

页数：6