Dadun Dadun cabecera universidad cabecera biblioteca
   (New user)
Help  | Contact  |  Castellano English  
 

Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Trombosis y hemostasia > DA - CIMA - Cardiovasculares - Trombosis y Hemostasia - Artículos de Revista >

Tumor necrosis factor-alpha inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock
Authors: Rodriguez-Wilhelmi, P. (Pablo)
Montes, R. (Ramón)
Matsukawa, A. (Akihiro)
Nariuchi, H. (Hideo)
Hurtado, V. (Verónica)
Montes, M. (Marta)
Hermida, J. (José)
Rocha, E. (Eduardo)
Keywords: Antibodies, Monoclonal/pharmacology
Fibrin/metabolism
Interleukin-8/metabolism
Shock, Septic/metabolism
Tumor Necrosis Factor-alpha/antagonists & inhibitors
Issue Date: 2003
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0022214302930398
ISSN: 1532-6543
Citation: Rodriguez-Wilhelmi P, Montes R, Matsukawa A, Nariuchi H, Hurtado V, Montes M, et al. Tumor necrosis factor-alpha inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock. J Lab Clin Med 2003 Apr;141(4):257-264.
Abstract
The effects of a monoclonal antibody (mAb) to tumor necrosis factor-alpha (TNF-alpha) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 microg/kg/hr) for 6 hours (n = 11) increased TNF-alpha levels. Fibrinogen was partially consumed, and fibrin deposits were seen in kidney and lungs at 24 hours. Mortality at 24 hours was 64%. Levels of interleukin-8 (aka CXCL-8) were notably increased. Mean arterial pressure (MAP) and leukocyte counts decreased, whereas creatinine levels were enhanced. The anti-TNF-alpha mAb (20 mg/kg i.v. bolus + 5 mg/kg/h i.v. for the first 90 minutes) (n = 10) efficiently inhibited the TNF-activity. Rabbits exhibited lower CXCL-8 levels; MAP improved, the decrease in leukocyte counts was partially prevented and creatinine levels were lower, but fibrinogen, fibrin deposits in kidneys and lungs and mortality, 55%, were similar to the LPS group. Rabbits that did not survive exhibited lower fibrinogen levels, more fibrin in kidneys and lungs and higher CXCL-8 and creatinine levels than survivors, while there were no differences in TNF-alpha, MAP and leukocytes. Thus, the inhibition of TNF-alpha, although beneficial through lowering CXCL-8 levels, is not enough to improve the outcome, which could be partly due to the inability to prevent the fibrin deposits formation in kidneys and lungs.
Permanent link: http://hdl.handle.net/10171/22117
Appears in Collections:DA - CIMA - Cardiovasculares - Trombosis y Hemostasia - Artículos de Revista

Files in This Item:
File:  JLabClinMed2003_1414257.pdf
Description: 
Size:  184,5 kB
Format:  Adobe PDF
 View / Open 

Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.