Attenuation of toll-like receptor 2-mediated innate immune response in patients with alcoholic chronic liver disease

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Pimentel-Nunes P (Author) FMUP; Roncon-Albuquerque R Jr (Author) FMUP; Gonçalves N (Author) FMUP; Fernandes-Cerqueira C (Author) Other; Cardoso H (Author) Other; Bastos RP (Author) Other; Marques M (Author) Other; Marques C (Author) Other; Alexandre-Sarmento J (Author) Other; Costa-Santos C (Author) Other; Macedo G (Author) Other; Pestana M (Author) Other; Dinis-Ribeiro M (Author) Other; Leite-Moreira AF (Author) FMUP

Journal

Title: Liver International

Vol. 30 No. 7

Pages: 1003-1011

ISSN: 1478-3223

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 21 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-4GE

DOI: 10.1111/j.1478-3231.2010.02251.x

Abstract (EN): Background: Alcoholic chronic liver disease (ACLD) is a common form of acquired immunodeficiency. Aim: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9