Relationship between the expression of Toll-like receptor 2 and 4 in mononuclear cells and postoperative acute lung injury in orthotopic liver transplantation

Abstract

Background: The aim of this study was to investigate the potential relationship between the dynamic expression of Toll-like receptor 2 and 4 (TLR2/4) in peripheral blood mononuclear cells as well as changes in serum concentration of inflammatory factors and acute lung injury (ALI) in patients after orthotopic liver transplantation (OLT).

Methods: The peripheral blood samples of 27 patients (23 men and 4 women with ASA III to IV) who received OLT were collected for measurement of TLR2/4 at T1 (after induction of anesthesia), T2 (25 minutes after anhepatic phase), T3 (3 hours after graft reperfusion) and T4 (24 hours after graft reperfusion). The expression of TLR2/4 in mononuclear cells was measured by flow cytometry. The serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). Twenty-seven patients were assigned to ALI group (n = 9) and non-ALI group (n = 18) according to the diagnostic criteria of ALI. The expression of TLR2/4 in the ALI group or non-ALI group was analyzed.

Results: Compared to the non-ALI group, the volumes of blood loss, ascites, total output and transfused red blood cells were higher in the ALI group, and the anhepatic phase lasted longer (P < 0.05, P < 0.01). The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4, and serum concentrations of TNF-alpha, IL-1beta and IL-8 increased significantly too. There was no significant difference in Child-Turcotte-Pugh (CTP) scores between the ALI group and non-ALI group (P > 0.05). The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4 in the ALI group (P < 0.05, P < 0.01). A positive correlation was noted between the expression of TLR4 in mononuclear cells and the serum concentrations of TNF-alpha, IL-1beta (P = 0.041, P = 0.046) in the ALI group. In the non-ALI group, statistical results showed that the expression level of TLR2/4 in mononuclear cells was not significantly different during the peri-operative period of OLT (besides TLR4 expression at T4). Compared to the non-ALI group, the increasing amplitude of TLR2/4 expression in mononuclear cells was more significant in the ALI group. The patients whose TLR2/4 expression in mononuclear cells exceeded that at T1 by one time were more likely to suffer from ALI (P = 0.013), with a relative risk of 16.

Conclusion: The expression level of TLR2/4 in mononuclear cells increases significantly in the peri-operative period of OLT, and it may be a high risk factor for occurrence of postoperative ALI.