Monoclonal antibody to endotoxin attenuates hemorrhage-induced lung injury and mortality in rats.
OBJECTIVE
To determine the possible role of enteric bacteria-derived endotoxin in the pathogenesis of the lung injury and mortality in rats following hemorrhagic shock and resuscitation.


METHODS
Prospective, randomized study.


METHODS
Animal laboratory of an institute for research traumatology.


METHODS
Male Sprague-Dawley rats, weighing 450 to 480 g.


METHODS
Anesthetized rats were subjected to a prolonged hemorrhagic shock (mean arterial pressure of 30 to 35 mm Hg for 180 mins) followed by resuscitation. A murine monoclonal antibody to lipopolysaccharide from Escherichia coli and Salmonella, WN1 222-5, was administered at a total dose of 5 mg/kg i.v., starting at the onset of shock (WN1 group). The control group was treated similarly to the WN1 group but received saline at the same volume as WN1 222-5.


RESULTS
The 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs. 78.6% in the control group; p = .0169). The characteristic lung injury in this model was significantly reduced in the WN1 group, as assessed by microscopic histopathologic examination increase in lung wet weight (7.60 +/- 0.47 g/kg in the control group vs. 5.14 +/- 0.31 g/kg in the WN1 group; p = .0002), and pulmonary neutrophilic infiltration (myeloperoxidase activity: 1835 +/- 567 mU/g wet weight in the control group vs. 891 +/- 212 mU/g wet weight in the WN1 group).


CONCLUSIONS
These data suggest that a) endotoxin derived from enteric bacteria might play an important role in the pathogenesis of lung injury; and b) antiendotoxin agents, such as WN1 222-5, appear to protect against endogenous bacterial endotoxin-related disorders in severe hemorrhagic shock in rats.
Bahrami
S
S
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Yao
Y M
YM
Leichtfried
G
G
Redl
H
H
Schlag
G
G
Di Padova
F E
FE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004731:Endotoxins / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D004731:Endotoxins