Presence of Plasma Endotoxin Is Correlated With Tumour Necrosis Factor Receptor Levels and Disease Activity in Alcoholic Cirrhosis

Hanck, C; Rossol, S.; Böcker, Ulrich; Tokus, Mehmet; Singer, Manfred V.

doi:10.1093/alcalc/33.6.606

Cited by 84 publications

(58 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These drawbacks are reflected in the rate of endotoxin detection in cirrhosis, which ranges from 0 to 93% in several studies. 6,[16][17][18][19][20] In the present study, elevated LBP levels identified a subset of ascitic cirrhotic patients with an exacerbated proinflammatory immune response and a more marked deranged hemody- namic status that could not be identified by elevated endotoxin levels. To avoid possible confounding factors, patients with recent complications of cirrhosis, recent bacterial infection, or current or past pathologic conditions with possible effects on the immune system were excluded.…”

Section: Discussionmentioning

confidence: 50%

“…Patients undergoing active alcohol ingestion were also excluded because alcoholism has been associated with increased intestinal permeability and endotoxinemia. 20,21 Endotoxin or endotoxin-containing particles (including intact gram-negative bacteria) form complexes with LBP and activate monocytes and tissue macrophages. This leads to the production of proinflammatory cytokines, release of sCD14, and further production of LBP.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

et al. 2003

View full text Add to dashboard Cite

Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 ؎ 0.7 versus 6.06 ؎ 0.5 g/mL, P < .01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P < .05) levels of sCD14, tumor necrosis factor ␣ (TNF-␣), interleukin 6 (IL-6), nitrites ؉ nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P < .01) LBP (from 16.6 ؎ 0.5 to 5.82 ؎ 0.8 g/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process. (HEPATOLOGY 2003;37:208-217.)

show abstract

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Serum tumour necrosis factor-alpha (TNF-a) levels are elevated in alcoholics (17), supporting the theory that Kupffer cells are activated in patients with alcoholic liver disease. In a recent study, plasma LPS, soluble TNF-a receptors and TNF-a were measured in patients who suffered from ethanol-induced cirrhosis (18). The data from this study were the first to report the strong correlation between plasma LPS and TNF-a soluble receptors in alcoholic cirrhosis.…”

Section: Role Of Gut-derived Lps In Ethanol-induced Injurymentioning

confidence: 74%

Sex‐Related Liver Injury Due to Alcohol Involves Activation of Kupffer Cells by Endotoxin

Thurman

1999

Canadian Journal of Gastroenterology and Hepatology

View full text Add to dashboard Cite

MINI-REVIEWRG Thurman. Sex-related liver injury due to alcohol involves activation of Kupffer cells by endotoxin. Can J Gastroenterol 2000;14(Suppl D):129D-135D. Females have a greater susceptibility to ethanol-induced liver injury than males. Females who drink ethanol regularly and have been overweight for 10 years or more are at greater risk for both hepatitis and cirrhosis than males, and females develop ethanol-induced liver injury more rapidly and with less ethanol than males. Female rats on an enteral ethanol protocol exhibit injury more quickly than males and have widespread fatty changes over a larger portion of the liver lobule. Moreover, levels of plasma endotoxin, intracellular adhesion molecule-1, free radical adducts, infiltrating neutrophils and nuclear factor kappa B are doubled in female rat livers compared with male rat livers after enteral ethanol treatment. Additionally, estrogen treatment in vivo increases the sensitivity of hepatic macrophages or Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are pivotal in the development of ethanol-induced liver injury. Destroying Kupffer cells with gadolinium chloride or decreasing bacterial endotoxin by sterilizing the gut with antibiotics inhibits early inflammation due to ethanol. Similar results have been obtained with anti-tumour necrosis factor-alpha antibody. These data pointed to the hypothesis that ethanol-induced liver injury involves elevations in circulating endotoxin concentrations leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury. This theory has been tested using pimonidazole, a 2-nitroimidazole marker, to quantify hypoxia in downstream, pericentral regions of the hepatic lobule. After chronic enteral ethanol treatment, pimonidazole binding doubles. Enteral ethanol also increases free radicals detected with electron spin resonance. Radical adducts, with coupling constants such as alpha-hydroxyethyl radical, have been shown to arise from ethanol. Importantly, hypoxia and radical production detected in bile are also decreased by the destruction of Kupffer cells with gadolinium chloride. These data support the hypothesis that Kupffer cells contribute to the vital sex differences in liver injury caused by ethanol. Des rates soumises à un protocole éthylique entérique manifestent une atteinte hépatique plus rapidement que les mâles et présentent des anomalies adipeuses réparties sur une portion plus importante du lobule hépatique. De plus, les taux d'endotoxines plasmatiques, de molé-cule 1 de l'adhésion, d'adduits des radicaux libres, de neutrophiles infiltrants et de facteur kappa B nucléaire se trouvent multipliés par deux dans les foies des rates si on les compare aux rats soumis au même traitement. En outre, le traitement oestrogénique in vivo accroît la sensibilité des macrophages du foie (ou cellules de Kupffer) aux endotoxines. Selon les preuves accumulées, les cellules de Kupffer sont essentielles au développement de l'atteinte hépati-que d'origine éthylique. La destruction d...

show abstract

“…In addition to ATP synthesis, mitochondria also regulate Ca 2ϩ signals through rapid accumulation or release of Ca 2ϩ (22). Although intracellular Ca 2ϩ plays a crucial role in cellular metabolism, mitochondrial Ca 2ϩ overload has been demonstrated to trigger ROS generation, mitochondrial dysfunction, and ATP depletion.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and metabolic stress induced by acetaldehyde in human intestinal LS174T goblet-like cells

Elamin

Masclee

Troost

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

) were assessed by dichlorofluorescein, methyltetrazolium, and bioluminescence, MitoTracker green and rhod-2 doublelabeling. Membrane integrity and apoptosis were evaluated by measuring lactate dehydrogenase (LDH), caspase 3/7, and cleavage of cytokeratin 18 (CK18). Expression of mucin 2 (MUC2) was determined by cell-based ELISA. Acetaldehyde significantly increased reactive oxygen species generation and decreased mitochondrial function compared with negative controls (P Ͻ 0.05). In addition, acetaldehyde dose-dependently decreased ATP levels and induced intramitochondrial Ca 2ϩ accumulation compared with negative controls (P Ͻ 0.05). Furthermore, acetaldehyde induced LDH release and increased caspase3/7 activity and percentage of cells expressing cleaved CK18 and increased MUC2 protein expression compared with negative controls (P Ͻ 0.0001). ATP depletion and LDH release could be largely prevented by the antioxidant N-acetylcysteine, suggesting a pivotal role for oxidative stress. Our data demonstrate that acetaldehyde has distinct oxidant-dependent metabolic and cytotoxic effects on LS174T cells that can lead to induction of cellular apoptosis. These effects may contribute to acetaldehyde-induced intestinal barrier dysfunction and subsequently to liver injury.

show abstract

Presence of Plasma Endotoxin Is Correlated With Tumour Necrosis Factor Receptor Levels and Disease Activity in Alcoholic Cirrhosis

Cited by 84 publications

References 12 publications

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

Sex‐Related Liver Injury Due to Alcohol Involves Activation of Kupffer Cells by Endotoxin

Cytotoxicity and metabolic stress induced by acetaldehyde in human intestinal LS174T goblet-like cells

Contact Info

Product

Resources

About