Objective: Toll-like receptors (TLR) 2 and 4 were shown recently to mediate lipopolysaccharide (LPS)/endotoxin effects in vivo. Absence of clinical features, such as fever and leucocytosis, frequent infections, and up-regulation of anti-inflammatory cytokines suggest systemic differential regulation of LPS effects in patients with chronic endotoxinaemia due to liver cirrhosis.
Design: Regulation of TLR2 and TLR4 represents a possible pathway to control LPS-induced immune responses in liver cirrhosis.
Methods: We compared the expression of TLR2 and TLR4 in peripheral blood mononuclear cells (PBMC) (n = 28) and in liver biopsies (n = 20) of controls and of patients with liver cirrhosis by applying the reverse transcriptase polymerase chain reaction technique. The data were correlated to serum levels of LPS and CD14.
Results: Expression of TLR2 was up-regulated (P < 0.01 to P < 0.05) in the PBMC of patients with high serum endotoxin levels, while TLR4 expression in patients at Child-Pugh stage A was down-regulated, irrespective of the origin (alcoholic or viral) of cirrhosis. A strong and significant correlation between expression of TLR2 and serum LPS (r = 0.638, P < 0.01) and soluble CD14 (r = 0.550, P < 0.05) was observed. Intrahepatic expression of TLR2/4 was not altered significantly in patients with liver cirrhosis.
Conclusion: Our data indicate LPS-driven regulation of TLR2/4 in patients with liver cirrhosis, suggesting involvement in mechanisms of systemic LPS hyporesponsiveness.