Document Detail

Evidence of neutrophil functional defect despite inflammation in stable cirrhosis.
MedLine Citation:
PMID:  21236309     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Deranged neutrophil function in alcoholic hepatitis has been shown to be transmissible to normal neutrophils by patient plasma. The aims of this study were (i) to evaluate whether patients with stable cirrhosis have a similar transmissible neutrophil defect and (ii) to explore the possible mechanisms.
METHODS: Plasma samples from 108 stable cirrhotic patients (Child A or B: 58; Child C: 50) and matched controls were incubated with normal neutrophils. Neutrophil resting respiratory burst, phagocytosis, and toll-like receptors 2, 4, and 9 expressions as well as plasma endotoxin, bacterial DNA, and cytokines were measured. In a separate study, eight patients and five controls were studied using a novel 'skin-window' technique to evaluate neutrophil function in an area of induced sterile inflammation.
RESULTS: Patient plasma induced neutrophil phagocytic dysfunction was greater in patients with more severe disease and was associated with increased expression of toll-like receptors 2 and 4. An increased resting respiratory burst was observed in a subset of patients, showing higher levels of inflammatory cytokines and more pronounced phagocytic impairment. No correlation was found with endotoxemia or bacterial DNA. In patients with compensated cirrhosis and apparently normal neutrophil function, the 'skin-window' study disclosed a severe phagocytic defect at the site of inflammation. Significantly higher levels of neutrophil elastase and IL-8 were found in the blister fluid.
CONCLUSIONS: Stable cirrhosis is characterized by neutrophil phagocytic dysfunction which may be subtle and only revealed in inflamed peripheral tissues where excessive inflammatory mediators continue to be released.
Giovanni Tritto; Zois Bechlis; Vanessa Stadlbauer; Nathan Davies; Rubén Francés; Naina Shah; Rajeshwar P Mookerjee; Jose Such; Rajiv Jalan
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Publication Detail:
Type:  Journal Article     Date:  2011-01-12
Journal Detail:
Title:  Journal of hepatology     Volume:  55     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-19     Completed Date:  2012-01-23     Revised Date:  2012-08-24    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  574-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK; Hepatology Unit, Cardarelli Hospital, Napoli, Italy.
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MeSH Terms
Cells, Cultured
Cytokines / blood
DNA, Bacterial / blood
Endotoxins / blood
Inflammation / immunology
Liver Cirrhosis / blood,  immunology*
Middle Aged
Neutrophils / immunology,  metabolism,  physiology*
Pancreatic Elastase / metabolism
Phagocytosis / physiology
Respiratory Burst / physiology
Skin Window Technique
Toll-Like Receptor 2 / metabolism
Toll-Like Receptor 4 / metabolism
Toll-Like Receptor 9 / metabolism
Reg. No./Substance:
0/Cytokines; 0/DNA, Bacterial; 0/Endotoxins; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Toll-Like Receptor 9; EC Elastase
Comment In:
J Hepatol. 2012 May;56(5):1212-3; author reply 1213-4   [PMID:  22127281 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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