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


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.
Tsujimoto
Hironori
H
Department of Surgery I, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. grd1523@ndmc.ac.jp
Ono
Satoshi
S
Majima
Takashi
T
Efron
Philip A
PA
Kinoshita
Manabu
M
Hiraide
Hoshio
H
Moldawer
Lyle L
LL
Mochizuki
Hidetaka
H
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000097:blood; D018805:Sepsis / Q000276:immunology*; D013514:Surgical Procedures, Operative / Q000009:adverse effects; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000097:blood; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000097:blood
D015703:Antigens, CD; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017452:Receptors, IgG; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors