| TAKEDA-143242 Increased Survival Via Reduced Cytokines in Porcine Peritonitis. | |
| | |
MedLine Citation:
|
PMID: 21236445 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
TAKEDA-143242 (TAK-242) is a small molecule shown to inhibit lipopolysaccharide-induced intracellular signaling and inflammation. In vitro studies demonstrated that TAK-242 can prevent release of TNF-α, IL-1β, and IL-6 from activated macrophages of several species, including pigs. This study tested the hypothesis that TAK-242 would protect pigs from lethal gram-negative peritonitis via an anti-cytokine mechanism. A validated model of porcine gram-negative peritonitis, which employs chronically inplantated cardiac transducers and aortic and pulmonary artery catheters, was used. Pigs were pretreated with TAK-242 or its vehicle via a blinding procedure prior to intraperitoneal implantation of an LD(90) dose of E. coli 0111:B4 in a fibrin clot. Ten pigs were treated with TAK-242 and nine with its vehicle. All ten TAK-242 treated pigs survived, while three of the nine vehicle treated pigs survived (P = 0.01 χ(2) test). Pulmonary artery pressure increased markedly in vehicle pigs, and this elevation was significantly (two-way ANOVA) obviated in TAK-242 treated group. Circulating levels of cytokines in vehicle treated pigs showed increased expression (3930 ± 1770 at 1 h, 1007 ± 400 TNF-α at 2 h; 719 ± 308 of IL-1β at 2-6 h; 33000 ± 1000 of IL-6 at 2-4 h [pg/mL, mean ± SEM]). Peak circulating levels of these cytokines were significantly reduced by pretreatment with TAK-242 (<25 pg/mL TNF-α ; <100 pg/mL IL-1β; 0-1700 pg/mL IL-6, peak values). This study found that pretreatment with TAK-242 yielded significantly positive survival benefit in a lethal sepsis model that was associated with improved cardiovascular status and suppressed cytokine release. |
| | |
Authors:
|
Roy D Goldfarb; John W Ortegel; Joseph E Parrillo; Sergio Zanotti-Cavazzoni; Larry C Casey; R Phillip Dellinger |
Related Documents
:
|
17488475 - E2f1 death pathways as targets for cancer therapy. 17005005 - Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for ... 16634895 - Cxc chemokine receptor cxcr4 expression enhances tumorigenesis and angiogenesis of basa... 21311075 - Unusual systemic signs in a dog with sterile neutrophilic-macrophagic lymphadenitis and... 19706765 - Matrix metalloproteinase 12 overexpression in lung epithelial cells plays a key role in... 20388085 - Inflammatory responses in embryonal cardiomyocytes exposed to lps challenge: an in vitr... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2010-11-11 |
Journal Detail:
|
Title: The Journal of surgical research Volume: - ISSN: 1095-8673 ISO Abbreviation: - Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2011-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Medicine, Sections of Cardiology and Critical Care, Rush Medical College, Chicago, Illinois. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Development of a Surgical Educational Research Program-Fundamental Principles and Challenges.
Next Document: Brain abnormalities in neuromyelitis optica.