Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic rat

Harry, David; Anand, Radhi; Holt, Stephen G; Davies, Susan; Marley, Richard; Fernando, Bimbi; Goodier, David; Moore, Kevin

doi:10.1002/hep.510300515

Cited by 99 publications

(105 citation statements)

References 49 publications

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“…These data confirm and extend previous studies in bdl ro- dents. 9,[11][12][13][14] In earlier studies in rodents, 9,10 we showed that endotoxin sensitivity is increased after bdl, and rises further when endotoxin transport to the cholestatic liver is increased by binding with (reconstituted) high density lipoprotein. 9 Humans with biliary obstruction also show evidence for enhanced susceptibility to endotoxin.…”

Section: Discussionmentioning

confidence: 79%

“…9 In addition, cholestasis is associated with enhanced susceptibility toward endotoxin-induced toxicity. [9][10][11][12][13][14] Endotoxin exerts its biological effects by activating immunocompetent cells such as monocytes and macrophages. After exposure to endotoxin, these cells readily release various inflammatory mediators such as the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), 15 which leads to an inflammatory response.…”

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confidence: 99%

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Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

et al. 2002

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Cholestatic liver injury is associated with an increased susceptibility toward endotoxininduced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R ؊/؊ ) mice, which are unresponsive to IL-1␣ and IL-1␤, and normal IL-1R ؉/؉ mice. Bdl elicited increases in hepatic IL-1␣ and IL-1␤ messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R ؊/؊ and IL-1R ؉/؉ mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in shamoperated IL-1R ؊/؊ and IL-1R ؉/؉ mice were largely similar, but cholestatic IL-1R ؊/؊ mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1␣ and IL-1␤ are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl. S urgery in jaundiced patients with periampullary tumors carries an increased risk of postoperative complications. 1 Whereas in experienced centers, postoperative mortality has been reduced from 20% to 5%, morbidity remains as high as 50%. 2,3 Most complications have a septic etiology and are considered to be related with translocation of endotoxin from the intestinal lumen into the portal and systemic circulation where an inflammatory cascade is triggered. 4,5 Potential causes of translocation of endotoxin include lack of bile salts in the intestinal lumen resulting in increased bacterial translocation, 6,7 decreased function of the resident macrophages of the liver (the Kupffer cells) leading to inadequate interception of endotoxin, 6-8 and changes in plasma concentrations of lipoproteins which bind endotoxin. 9 In addition, cholestasis is associated with enhanced susceptibility toward endotoxin-induced toxicity. [9][10][11][12][13][14] Endotoxin exerts its biological effects by activating immunocompetent cells such as monocytes and macrophages. After exposure to endotoxin, these cells readily release various inflammatory mediators such as the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), 15 which leads to an inflammatory response. The Kupffer cells are also capable of releasing these cytokines in response to endotoxin. 16,17 IL-1␣ and IL-1␤ are pleiotropic proinflammatory cytokines that are considered to play a proximal role in initiation and regulation of the inflammatory cascade triggered in response to endotoxins or bacteremia. 15,18 Both IL-1␣ and IL-1␤ can interact with two specific cell surface receptors, the type I and type II IL-1 receptor (IL-1R), of ...

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Section: Discussionmentioning

confidence: 79%

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confidence: 99%

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

et al. 2002

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“…In contrast, previous papers reported that BDL mice produced a large amount of TNF-␣ after LPS stimulation. 11,32 This may reflect a difference of LPS versus whole bacterial challenge. In fact, we found in our experimental model that serum TNF-␣ levels of BDL mice were more than 10 times higher than those of sham-operated mice 1 hour after 4 mg/kg LPS injection (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…9,10 It is also demonstrated that rats and mice with experimental obstructive jaundice produce higher levels of proinflammatory cytokines including TNF-␣, IL-1, and IL-6 after lipopolysaccharide (LPS) injection compared with those without obstructive jaundice, and that cholestatic animals are susceptible to LPS-induced organ failure and mortality. [11][12][13] However, involvement of anti-inflammatory cytokines in host resistance to bacterial infection in cholestasis or cy-tokine profile in response to exogenously administered viable bacteria in cholestatic animals remains to be elucidated.…”

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confidence: 99%

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

et al. 2004

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Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and-most importantly-postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 10 7 colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon ␥ production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fasmediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells. (HEPATOLOGY 2004;40:414 -423.)

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“…Liver specimens were collected at 5 h after LPS injection, at the end of the experiments. The LPS treatment concentration was set at 5 ㎎/㎏ based on the finding that this concentration has been shown to cause endotoxin shock in rats and mice over a short period of time, raising the cytokine concentrations in the liver and blood (Corral et al, 1996;Aono et al, 1997;Harry et al, 1999;Sang et al, 1999).…”

Section: Animal Experimentsmentioning

confidence: 99%

Anti-inflammatory Effects of Allium victorialis Extract in Lipopolysaccharide Exposed Rats and Raw 264.7 Cells

Lee¹

2014

Korean Journal of Plant Resources

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-This study examined the inflammatory reaction effects of Allium victorialis var. platyphyllum in vivo at the time of a lipopolysaccharide (LPS) shock in rats, and in vitro in cultured Raw 264.7 cells, with the aim of facilitating the development of a new anti-inflammatory medicine. Plasma concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and IL-10 in rats peaked 5 h after LPS treatment in all experimental groups, with those of IL-1β, IL-6, and TNF-α being significantly lower in all animals treated with A. victorialis than in the control group at that time point. Conversely, the plasma concentration of IL-10 was higher in the rats treated with 300 ㎎/㎏ A. victorialis extract than in the control group at both 2 and 5 h after LPS treatment. Concentrations of IL-1β and IL-6 in the liver of rats treated with A. victorialis extract were significantly lower than those of the saline-treated control group. However, the liver concentrations of TNF-α and IL-10 did not vary significantly between the four animal groups. Similarly, concentrations of IL-1β, IL-6, and TNF-α obtained from cultured Raw 264.7 macrophages were lower in all of the A.-victorialis-extract-treated groups than in the control group. Although the concentration of IL-10 in the A.-victorialis-extract-treated groups tended to be greater than in the control group, the differences between groups were not statistically significant. Together the findings of this study suggest that A. victorialis var. platyphyllum contains functional substances that are involved in inflammatory reactions.

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Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic rat

Cited by 99 publications

References 49 publications

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

Anti-inflammatory Effects of Allium victorialis Extract in Lipopolysaccharide Exposed Rats and Raw 264.7 Cells

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