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 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.
Smith
Lincoln S
LS
Division of Pediatric Critical Care, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
Kajikawa
Osamu
O
Elson
Greg
G
Wick
Merry
M
Mongovin
Steve
S
Kosco-Vilbois
Marie
M
Martin
Thomas R
TR
Frevert
Charles W
CW
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D016209:Interleukin-8 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D011817:Rabbits; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4