title: Attenuation of toll-like receptor 2-mediated innate immune response in patients with alcoholic chronic liver disease.
abstract: BACKGROUND
  Alcoholic chronic liver disease (ACLD) is a common form of acquired immunodeficiency.
  
  
  OBJECTIVE
  To evaluate ex vivo toll-like receptor (TLR) 2 and TLR4 innate immune response in stable ACLD.
  
  
  METHODS
  Blood was collected from 26 males with stable ACLD and from 17 controls. Serum was used for lipopolysaccharide (LPS), sCD14, LPS-binding protein (LBP), tumour necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) quantification. Peripheral blood monocytes (PBM) protein expression of TLR2 and TLR4 was determined by flow cytometry. Primary cultures of anti-CD11b positive selected PBM were stimulated with the TLR2/TLR6 ligand zymosan (Zym), with TLR2/TLR1 ligand lipopeptide (Lp) and with TLR4 ligand LPS. PBM TLR1, TLR2, TLR4, TLR6, MD2, CD14, TNF-alpha and IL-10 gene expression was evaluated by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Stable ACLD patients showed increased circulating LPS (+22.5+/-4.1%), LBP (+60.6+/-12.2%) and sCD14 (+23.5+/-4.6%), with no differences in TNF-alpha and IL-10. Zym and Lp, but not LPS, induced TNF-alpha production by monocytes was blunted in ACLD (-66+/-20.4% Zym; -40.1+/-13.5% Lp; P<0.05). Basal TNF-alpha mRNA expression was decreased in PBM from ACLD patients (-50.1+/-21.0%; P<0.05), with no significant differences in the other studied genes. Results were similar in Child-Pugh A and B/C patients.
  
  
  CONCLUSIONS
  Patients with stable ACLD show an attenuation of TLR2-mediated innate immune response in PBM, which may represent an important mechanism for acquired immunodeficiency. This was neither related with decreased TLR2 or its co-receptors expression nor with impaired TLR4 activation, being already present in the early stages of disease.
authors.affiliation: Department of Physiology, Cardiovascular Research & Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Pimentel-Nunes
authors.forename: Roberto
authors.initials: R
authors.lastname: Roncon-Albuquerque
authors.forename: Nádia
authors.initials: N
authors.lastname: Gonçalves
authors.forename: Cátia
authors.initials: C
authors.lastname: Fernandes-Cerqueira
authors.forename: Hélder
authors.initials: H
authors.lastname: Cardoso
authors.forename: Rui Pedro
authors.initials: RP
authors.lastname: Bastos
authors.forename: Margarida
authors.initials: M
authors.lastname: Marques
authors.forename: Cristina
authors.initials: C
authors.lastname: Marques
authors.forename: José
authors.initials: J
authors.lastname: Alexandre Sarmento
authors.forename: Carlos
authors.initials: C
authors.lastname: Costa-Santos
authors.forename: Guilherme
authors.initials: G
authors.lastname: Macedo
authors.forename: Manuel
authors.initials: M
authors.lastname: Pestana
authors.forename: Mário
authors.initials: M
authors.lastname: Dinis-Ribeiro
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000209:Acute-Phase Proteins; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D055666:Lipopeptides / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D011174:Portugal; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000097:blood* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015054:Zymosan / Q000494:pharmacology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016753:Interleukin-10; D055666:Lipopeptides; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D000099231:Lipopolysaccharide-Binding Protein; C508609:IL10 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human