Citation

Lundeland B, Gundersen Y, Opstad PK, Thrane I, Zhang Y, Olaussen RW, Vaagenes P. Acta Anaesthesiol. Scand. 2011; 55(1): 28-34.

Affiliation

Institute of Clinical Medicine, University of Oslo, Oslo, Norway Division of Protection, Norwegian Defence Research Establishment, Kjeller, Norway Department of Anaesthesiology, Akershus University Hospital, Lørenskog, Norway Institute of Clinical Epidemiology and Molecular Biology, Akershus University Hospital, Lørenskog, Norway Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ullevål, Oslo, Norway.

Copyright

(Copyright © 2011, Acta Anaesthesiologica Scandinavica Foundation, Publisher John Wiley and Sons)

DOI

10.1111/j.1399-6576.2010.02351.x

PMID

21059178

Abstract

Background: The mechanisms behind lipopolysaccharide (LPS) tolerance remain obscure. LPS signals through Toll-like receptor 4 (TLR4) and severe trauma/haemorrhage may influence binding and signalling through this receptor, e.g. by changing membrane expression or by releasing endogenous ligands like High Mobility Group Box 1 (HMGB1). The aim of this study was to examine these relations further in a porcine model with standardized trauma. Methods: Nine anaesthetized pigs sustained one gunshot through the femur and one pistol shot through the upper abdomen. Blood was sampled before and 90 min after shooting. The samples were stimulated for 4 h with LPS 10 ng/ml or an equivalent amount of normal saline. The leucocyte response was evaluated by measuring the tumour necrosis factor-α (TNF-α) and CXC ligand 8 (CXCL8) in the supernatant. Flow cytometry was used to measure the surface expression of TLR4 on CD14+ monocytes. HMGB1 concentrations were measured in the plasma. Results: Trauma and treatment caused a significant decline in the LPS-stimulated concentrations of TNF-α [4.53 ± 0.24 pg/ml (ln) at 0 min, 3.54 ± 0.35 pg/ml (ln) at 90 min, P=0.026], but did not modify the release of CXCL8. Monocyte TLR4 expression was unchanged. Plasma HMGB1 increased significantly [<0.92 vs. 3.02 ± 0.19 ng/ml (ln), P<0.001]. The concentrations of TNF-α and CXCL8 did not correlate with TLR4 expression or HMGB1 concentrations. Conclusion: The results suggest that trauma-induced LPS tolerance is not primarily regulated by TLR4 expression on circulating CD14+ monocytes or by the release of HMGB1 from damaged tissues.

Language: en