Abstract
Background: Alcoholic chronic liver disease (ACLD) is one of the most common forms 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 ACLD in an outpatient hepatology clinic and from 10 controls. Serum was used for lipopolysaccharide (LPS), sCD14, LPS-binding protein(LBP), tumour necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) quantification. mRNA expression of TLR2, TLR4, MD2, CD14, TNF-α and IL-10 was evaluated in anti-CD11b positive selected monocytes. Monocyte primary cultures were stimulated with zymosan (TLR2 agonist) or LPS (TLR4 agonist), and TNF-α production analyzed. Results: ACLD patients presented increased circulating LPS (+22.5±4.1%), LBP (+60.6±12.2%) and sCD14 (+23.5±4.6%), but with no differences in TNF-α and IL-10. TNF-αmRNA expression was decreased in monocytes from ACLD patients (-50.1±8.0%), with no significant differences in the other studied genes. Zymosan, but not LPS, induced TNF-α production by monocytes was blunted in ACLD (-55.2±10.9%). Results were similar in Child-Pugh A and B/C patients. See figure *=p<0.05 vs control group; #= p<0.05 vs production at time 0h. Conclusions: Patients with ACLD present an attenuation of TLR2-mediated innate immune response. This was not related with decreased monocyte TLR2 expression or impaired TLR4 signaling pathways, being already present in the early stages of disease. Attenuation of TLR2 activation may constitute a mechanism for acquired immunodeficiency.
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