title: Evidence of neutrophil functional defect despite inflammation in stable cirrhosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK; Hepatology Unit, Cardarelli Hospital, Napoli, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tritto
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK.
authors.forename: Zois
authors.initials: Z
authors.lastname: Bechlis
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK; Medical University of Graz, Austria.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stadlbauer
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK.
authors.forename: Nathan
authors.initials: N
authors.lastname: Davies
authors.affiliation: Hospital General Universitario de Alicante, Centro de Investigación Biomédica en Red (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK.
authors.forename: Naina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK.
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.affiliation: Hospital General Universitario de Alicante, Centro de Investigación Biomédica en Red (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Such
authors.affiliation: Liver Failure Group, UCL Hepatology, Royal Free Hospital, London, UK. Electronic address: r.jalan@ucl.ac.uk.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004269:DNA, Bacterial / Q000097:blood; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D016897:Respiratory Burst / Q000502:physiology; D012884:Skin Window Technique; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D016207:Cytokines; D004269:DNA, Bacterial; D004731:Endotoxins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D010196:Pancreatic Elastase