EFFECT OF TOLL-LIKE RECEPTOR 4 BLOCKADE ON PULMONARY INFLAMMATION CAUSED BY MECHANICAL VENTILATION AND BACTERIAL ENDOTOXIN

Mechanical ventilation (MV) and lipopolysaccharide (LPS) synergistically increase inflammation and lung injury. The goal of this study was to determine whether blockade of CD14 or Toll-like receptor 4 (TLR4) would reduce inflammation caused by LPS and MV. Rabbits were pretreated with anti-TLR4 or an...

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Bibliographic Details
Published in:Experimental lung research 2008-06, Vol.34 (5), p.225-243
Main Authors: Smith, Lincoln S., Kajikawa, Osamu, Elson, Greg, Wick, Merry, Mongovin, Steve, Kosco-Vilbois, Marie, Martin, Thomas R., Frevert, Charles W.
Format: Article
Language:English
Subjects:
acute lung injury
Animals
Antibodies, Blocking - pharmacology
Antibodies, Monoclonal - pharmacology
antibody blockade
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
CD14
Disease Models, Animal
Escherichia coli - immunology
Female
inflammation
innate immunity
Interleukin-8 - metabolism
lipopolysaccharide
Lipopolysaccharide Receptors - immunology
Lipopolysaccharide Receptors - metabolism
Lipopolysaccharides - toxicity
Lung - drug effects
Lung - metabolism
Lung - pathology
mechanical ventilation
Neutrophils - drug effects
Rabbits
Respiration, Artificial - adverse effects
Respiratory Distress Syndrome, Adult - etiology
Respiratory Distress Syndrome, Adult - metabolism
Respiratory Distress Syndrome, Adult - physiopathology
Specific Pathogen-Free Organisms
TLR4
toll-like receptor 4
Toll-Like Receptor 4 - antagonists & inhibitors
Toll-Like Receptor 4 - immunology
Toll-Like Receptor 4 - metabolism
ventilator-induced lung injury
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Summary:Mechanical ventilation (MV) and lipopolysaccharide (LPS) synergistically increase inflammation and lung injury. The goal of this study was to determine whether blockade of CD14 or Toll-like receptor 4 (TLR4) would reduce inflammation caused by LPS and MV. Rabbits were pretreated with anti-TLR4 or anti-CD14 monoclonal antibodies, followed by endobronchial LPS and MV. Blockade of TLR4 reduced the number of neutrophils and the amount of CXCL8 in bronchoalveolar lavage fluid. In contrast, blockade of CD14 did not significantly decrease the number of neutrophils or the amount of CXCL8. These data show that TLR4 blockade reduces pulmonary inflammation caused by the combination of LPS and Mechanical ventilation.
ISSN:0190-2148
1521-0499
DOI:10.1080/01902140802022492