title: Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase.
abstract: BACKGROUND
  Alcoholic hepatitis is characterised by florid hepatic inflammation, liver failure, and death within 28 days in 35% of patients. We recently showed proliferative peripheral blood mononuclear cell (PBMC) responses to alcohol dehydrogenase (ADH) in patients with alcohol-related cirrhosis, associated with T-helper-type 1 (Th1) immunity and disease severity. We aimed to define whether ADH-specific cellular immunity is present in alcoholic hepatitis.
  
  
  METHODS
  PBMCs were collected from 15 patients with alcoholic hepatitis (modified Maddrey's discriminant function >32), nine with alcohol-related cirrhosis (long-term alcohol abstinence), and three healthy controls. 25 overlapping peptides, spanning the human ADH β1 subunit, were constructed. Proliferation to ADH peptides (1 × 10(5) cells per well, cultured with 10 mM peptides for 7 days) was assessed by (3)H-thymidine incorporation. A stimulation index (SI) of 2·5 or more was regarded as positive. ELISA measured concentrations of interferon γ (IFNγ), interleukin (IL) 17, and IL4 from supernatant.
  
  
  RESULTS
  PBMCs from seven of 15 patients with alcoholic hepatitis recognised one to three ADH peptides (SI ≤5·7). IFNγ (mean 390·9 pg/mL [SE 31·4]) was detected in 48% of wells, IL17 (20·1 [3 ·4]) in 15%, and IL4 (90·5 [9·3]) in 14%. PBMCs from six of the nine patients with alcohol-related cirrhosis recognised one to five peptides (SI ≤5·2). IFNγ (360·7 [58·9], p>0·05) was detected in 31% of wells, IL17 (57·7 [10·9], p=0·0006) in 19%, and IL4 (219·7 [11·2], p=0·0012) in 28%. PBMCs from two healthy controls recognised one to two peptides (SI ≤3·1); all cytokine levels were below baseline.
  
  
  CONCLUSIONS
  Proliferative anti-ADH immune responses in alcoholic hepatitis focused on individual epitopic regions. Predominance of proinflammatory Th1 responses was more pronounced in alcoholic hepatitis than in alcoholic-related cirrhosis. This finding requires investigation of targeted therapies to inhibit Th1 immunity in alcoholic hepatitis.
  
  
  BACKGROUND
  Wellcome Trust.
authors: Institute of Liver Studies & Transplantation, King's College London, London, UK. Electronic address: laura.blackmore@kcl.ac.uk.
authors: Laura J
authors: LJ
authors: Blackmore
authors: Institute of Liver Studies & Transplantation, King's College London, London, UK.
authors: Jennifer M
authors: JM
authors: Ryan
authors: Institute of Liver Studies & Transplantation, King's College London, London, UK.
authors: Xiaohong
authors: X
authors: Huang
authors: Institute of Liver Studies & Transplantation, King's College London, London, UK.
authors: Munther
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authors: Hussain
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authors: Evangelos
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authors: Triantafyllou
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authors: Nikhil
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authors: Vergis
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authors: Godhev Manakkat
authors: GM
authors: Vijay
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authors: Diego
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authors: Debbie L
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authors: Yun
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