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

Clin Immunol. 2006 May;119(2):180-7. doi: 10.1016/j.clim.2006.01.004. Epub 2006 Mar 6.

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 microg/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 TNFalpha and IL-1beta production in PBMCs from surgical patients, LPS-stimulation decreased IL-1beta 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antigens, CD / biosynthesis
  • Antigens, CD / blood
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Female
  • GPI-Linked Proteins
  • HLA-DR Antigens / biosynthesis
  • HLA-DR Antigens / blood
  • Humans
  • Inflammation Mediators / blood
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharide Receptors / biosynthesis
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharides / immunology*
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Receptors, IgG / biosynthesis
  • Receptors, IgG / blood
  • Sepsis / immunology*
  • Surgical Procedures, Operative* / adverse effects
  • Toll-Like Receptor 2 / biosynthesis
  • Toll-Like Receptor 2 / blood
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / blood
  • Toll-Like Receptors / biosynthesis*
  • Toll-Like Receptors / blood

Substances

  • Antigens, CD
  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • HLA-DR Antigens
  • Inflammation Mediators
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Receptors, IgG
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors