Tumor necrosis factor-α inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock

Pablo Rodriguez-Wilhelmi, Ramon Montes, Akihiro Matsukawa, Hideo Nariuchi, Veronica Hurtado, Marta Montes, Jose Hermida, Eduardo Rocha

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The effects of a monoclonal antibody (mAb) to tumor necrosis factor-α (TNF-α) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 μg/kg/hr) for 6 hours (n = 11) increased TNF-α 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-α 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-α, MAP and leukocytes. Thus, the inhibition of TNF-α, 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.

Original languageEnglish
Pages (from-to)257-264
Number of pages8
JournalJournal of Laboratory and Clinical Medicine
Volume141
Issue number4
DOIs
Publication statusPublished - Apr 1 2003
Externally publishedYes

Fingerprint

Septic Shock
Fibrin
Tumor Necrosis Factor-alpha
Rabbits
Fibrinogen
Kidney
Creatinine
Lung
Arterial Pressure
Deposits
Leukocyte Count
Monoclonal Antibodies
Mortality
Interleukin-8
Intravenous Administration
Lipopolysaccharides
Survivors
Leukocytes

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Tumor necrosis factor-α inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock. / Rodriguez-Wilhelmi, Pablo; Montes, Ramon; Matsukawa, Akihiro; Nariuchi, Hideo; Hurtado, Veronica; Montes, Marta; Hermida, Jose; Rocha, Eduardo.

In: Journal of Laboratory and Clinical Medicine, Vol. 141, No. 4, 01.04.2003, p. 257-264.

Research output: Contribution to journalArticle

Rodriguez-Wilhelmi, Pablo ; Montes, Ramon ; Matsukawa, Akihiro ; Nariuchi, Hideo ; Hurtado, Veronica ; Montes, Marta ; Hermida, Jose ; Rocha, Eduardo. / Tumor necrosis factor-α inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock. In: Journal of Laboratory and Clinical Medicine. 2003 ; Vol. 141, No. 4. pp. 257-264.
@article{4dd2a330882d4084b5a8858718f870df,
title = "Tumor necrosis factor-α inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock",
abstract = "The effects of a monoclonal antibody (mAb) to tumor necrosis factor-α (TNF-α) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 μg/kg/hr) for 6 hours (n = 11) increased TNF-α 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-α 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-α, MAP and leukocytes. Thus, the inhibition of TNF-α, 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.",
author = "Pablo Rodriguez-Wilhelmi and Ramon Montes and Akihiro Matsukawa and Hideo Nariuchi and Veronica Hurtado and Marta Montes and Jose Hermida and Eduardo Rocha",
year = "2003",
month = "4",
day = "1",
doi = "10.1067/mlc.2003.32",
language = "English",
volume = "141",
pages = "257--264",
journal = "Translational Research",
issn = "1931-5244",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Tumor necrosis factor-α inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock

AU - Rodriguez-Wilhelmi, Pablo

AU - Montes, Ramon

AU - Matsukawa, Akihiro

AU - Nariuchi, Hideo

AU - Hurtado, Veronica

AU - Montes, Marta

AU - Hermida, Jose

AU - Rocha, Eduardo

PY - 2003/4/1

Y1 - 2003/4/1

N2 - The effects of a monoclonal antibody (mAb) to tumor necrosis factor-α (TNF-α) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 μg/kg/hr) for 6 hours (n = 11) increased TNF-α 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-α 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-α, MAP and leukocytes. Thus, the inhibition of TNF-α, 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.

AB - The effects of a monoclonal antibody (mAb) to tumor necrosis factor-α (TNF-α) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 μg/kg/hr) for 6 hours (n = 11) increased TNF-α 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-α 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-α, MAP and leukocytes. Thus, the inhibition of TNF-α, 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.

UR - http://www.scopus.com/inward/record.url?scp=0344127553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344127553&partnerID=8YFLogxK

U2 - 10.1067/mlc.2003.32

DO - 10.1067/mlc.2003.32

M3 - Article

C2 - 12677171

AN - SCOPUS:0344127553

VL - 141

SP - 257

EP - 264

JO - Translational Research

JF - Translational Research

SN - 1931-5244

IS - 4

ER -