PMID- 18848768 OWN - NLM STAT- MEDLINE DCOM- 20091203 LR - 20151119 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 63 IP - 7 DP - 2009 Aug TI - Soluble TNFR II/IgG1 Fc fusion protein treatment in the LPS-mediated septic shock of rats. PG - 537-42 LID - 10.1016/j.biopha.2008.08.012 [doi] AB - 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-quantitative RT-PCR. sTNFR:Fc administered to rats 24h 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. FAU - Guo, Zhuying AU - Guo Z AD - Experimental Center, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 280, Baoshan District, Shanghai 201900, China. zyguoo@126.com FAU - Wang, Shiting AU - Wang S FAU - Jiao, Qiang AU - Jiao Q FAU - Xu, Manghua AU - Xu M FAU - Xu, Zhimei AU - Xu Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080916 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Immunoglobulin G) RN - 0 (Immunologic Factors) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - OP401G7OJC (Etanercept) SB - IM MH - Animals MH - Blood Pressure/drug effects MH - Etanercept MH - Humans MH - Immunoglobulin G/*therapeutic use MH - Immunologic Factors/*therapeutic use MH - Lipopolysaccharides/pharmacology MH - Liver/metabolism MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Tumor Necrosis Factor/*therapeutic use MH - Shock, Septic/*drug therapy/mortality/physiopathology MH - Survival Rate MH - Tumor Necrosis Factor-alpha/biosynthesis/blood/genetics EDAT- 2008/10/14 09:00 MHDA- 2009/12/16 06:00 CRDT- 2008/10/14 09:00 PHST- 2008/07/16 00:00 [received] PHST- 2008/08/24 00:00 [accepted] PHST- 2008/10/14 09:00 [pubmed] PHST- 2009/12/16 06:00 [medline] PHST- 2008/10/14 09:00 [entrez] AID - S0753-3322(08)00300-4 [pii] AID - 10.1016/j.biopha.2008.08.012 [doi] PST - ppublish SO - Biomed Pharmacother. 2009 Aug;63(7):537-42. doi: 10.1016/j.biopha.2008.08.012. Epub 2008 Sep 16.