Effect of hemorrhagic shock on endotoxin-induced TNF production and its molecular mechanism in rats

The present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) lipopolysaccharide (LPS) and its cellular source after hemorrhagic shock (HS) in rats, and to further analyze the mechanism for increased sensitivity to LPS through looking at expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs and kidneys. It was found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than that in the HS group (P < 0.01), and 2.7-fold higher than that in the LPS group (P < 0.05). It was shown in vitro that the capacity of peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (P < 0.01) and 57% (P < 0.05) compared with pre-shock levels and the sham group respectively at the end of resuscitation following shock, and was still markedly decreased 3 hours after resuscitation, while the capacity of Kupffer cells was significantly increased by 110% compared with the sham group (P < 0.01) after shock and resuscitation. Results from RT-PCR showed that expression of LBP mRNA in the liver, lungs and kidneys was increased after shock and resuscitation. It is suggested that hemorrhagic shock could significantly enhance endotoxin-induced TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and tissue macrophages might be the main source of cytokine production.