Heterozygous toll-like receptor 4 polymorphism does not influence lipopolysaccharide-induced cytokine release in human whole blood.
The heterozygous Asp299Gly mutation of the toll-like receptor (TLR) 4, the key receptor for lipopolysaccharide (LPS), has been associated with attenuated inflammatory responses. When 160 healthy volunteers (9% heterozygous and 0.6% homozygous) were genotyped and their LPS-inducible cytokine release was assessed in an ex vivo whole blood test, the responses of heterozygotes did not differ significantly from those of wild-type carriers for any of the cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, interferon-gamma, and granulocyte colony-stimulating factor) or eicosanoids measured or for serum cytokines and C-reactive protein. Ten heterozygous subjects and 12 wild-type control subjects responded similarly to a graded series of LPS and Escherichia coli concentrations, excluding the possibility that allele-specific differences are evident only at low stimulus concentrations or in response to whole pathogens. These data demonstrate that the heterozygous Asp299Gly polymorphism does not exhibit a functional defect in cytokine release after the stimulation of blood monocytes.
von Aulock
Sonja
S
Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
Schröder
Nicolas W J
NW
Gueinzius
Katja
K
Traub
Stephanie
S
Hoffmann
Sebastian
S
Graf
Kathrin
K
Dimmeler
Stefanie
S
Hartung
Thomas
T
Schumann
Ralf R
RR
Hermann
Corinna
C
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006579:Heterozygote; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012475:Salmonella / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors