title: Effect of hemorrhagic shock on endotoxin-inducing TNF production and intra-tissue lipopolysaccharide-binding protein mRNA expression and their relationship.
abstract: In order to further elucidate effect of hemorrhagic shock on endotoxin-inducing cytokine production, the present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) of lipopolysaccharide (LPS) and its cellular sources after hemorrhagic shock (HS) in rats. With combination of expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs, and kidneys, we further analyzed a possible mechanism for increasing sensitivity to LPS by shock. We found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than those in the HS group (p < .01) and 2.7-fold higher than those in the LPS group (p < .05). It was shown in vitro that the capacity of the peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (p < .01) and 57% (p < .05) compared with the pre-shock levels and sham group, respectively, at the end of resuscitation following shock, and still markedly inhibited 3 h after resuscitation, while the capacity of hepatic Kupffer's cells to produce TNF alpha was significantly increased by 110% compared with the sham group (p < .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 strengthen endotoxin to induce TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and the tissue macrophage population may be the main source for cytokine production in shock.
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: J X
authors.initials: JX
authors.lastname: Jiang
authors.forename: Y F
authors.initials: YF
authors.lastname: Diao
authors.forename: K L
authors.initials: KL
authors.lastname: Tian
authors.forename: H S
authors.initials: HS
authors.lastname: Chen
authors.forename: P F
authors.initials: PF
authors.lastname: Zhu
authors.forename: Z G
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004731:Endotoxins / Q000633:toxicity*; D015870:Gene Expression; D007668:Kidney / Q000737:chemistry; D007728:Kupffer Cells / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008562:Membrane Glycoproteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein