Differential toll-like receptor expression after ex vivo lipopolysaccharide exposure in patients with sepsis and following surgical stress

Abstract

Introduction: Monocytes from septic patients have a reduced capacity to respond to lipopolysaccharide (LPS). We examined whether the same response occurred after surgical injury, and whether this reduced activity was associated with differential monocyte toll-like receptor (TLR) expression. Materials and methods: Peripheral blood mononuclear cells (PBMCs) were isolated from septic patients, patients undergoing surgery, and healthy volunteers. Cells were stimulated ex vivo with LPS (1 μg/ml) and stained for CD14, CD16, TLR-2, TLR-4, and HLA-DR surface expression. Results: TLR-2 and -4 expressions were significantly increased in monocytes from both septic and surgical patients. While ex vivo LPS-stimulation significantly increased TNFα and IL-1β production in PBMCs from surgical patients, LPS-stimulation decreased IL-1β production from septic patients as compared to surgical and control patients. Ex vivo LPS-stimulation induced TLR-4 upregulation in monocytes from both surgical and control patients, but not from septic patients. HLA-DR expression in CD14 +CD16 + monocytes was reduced only in septic patients. Conclusions: PBMCs from septic patients, but not following surgical injury, have a reduced capacity to respond to a secondary inflammatory signal, but this defect is not associated with reduced TLR-4 or CD14 expression.