M1723 Highly Sensitive Metabolome Analysis of Cholesterol and Bile Acid Biosynthetic Pathways By LC-ESI-MS/MS

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