Differential expression of toll-like receptors 2 and 4 in patients with liver cirrhosis

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 in patients with liver cirrhosis, suggesting involvement in mechanisms of systemic LPS hyporesponsiveness.