To determine the possible mechanisms underlying beneficial effect of recombinant
bactericidal/permeability-increasing protein (rBPI) on
acute lung injury response to blood loss, we used reverse transcription polymerase chain reaction to measure pulmonary
tumor necrosis factor (TNF),
interleukin 6 (IL-6)
mRNA expression in a rat model of prolonged
hemorrhagic shock (4.00 kPa, 180 min) followed by adequate
resuscitation. The results showed that systemic plasma
endotoxin concentrations elevated rapidly after a 180-min hemorrhagic insult (P < 0.05), and TNF,
IL-6 mRNA expression in the lung were significantly increased at 2, 8 hours after
resuscitation respectively. However, treatment with rBPI resulted in almost neutralization of plasma
endotoxin values, remarkable reduction of TNF,
IL-6 mRNA levels following
hemorrhage/
resuscitation. Also, it was found that rBPI administration markedly blunted the increase in pulmonary
Evans blue dye extravasation, concomitant with a significant decrease in lung
myeloperoxidase activity compared with the control group (P < 0.05-0.01). These data suggest that local proinflammatory
cytokine mRNA expression associated with gut origin
endotoxemia may be an important mechanism contributing to the development of
hemorrhage-induced
lung injury. Treatment with rBPI is effective in inhibiting marked TNF,
IL-6 mRNA expression and ameliorating
acute lung injury secondary to severe
hemorrhagic shock.