Monoclonal antibody to endotoxin attenuates hemorrhage-induced lung injury and mortality in rats

Objectives: 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. Design: Prospective, randomized study. Setting: Animal laboratory of an institute for research in traumatology. Subjects: Male Sprague-Dawley rats, weighing 450 to 480 g. Interventions: 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 iv, 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. Measurements and Main Results: the 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs, 98.6% 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.