TY - JOUR
T1 - Heterozygous toll-like receptor 4 polymorphism does not influence lipopolysaccharide-induced cytokine release in human whole blood
AU - Von Aulock, Sonja
AU - Schröder, Nicolas W.J.
AU - Gueinzius, Katja
AU - Traub, Stephanie
AU - Hoffmann, Sebastian
AU - Graf, Kathrin
AU - Dimmeler, Stefanie
AU - Hartung, Thomas
AU - Schumann, Ralf R.
AU - Hermann, Corinna
PY - 2003/9/15
Y1 - 2003/9/15
N2 - The heterozygous Asp299Gly mutation of the toll-like receptor (TLR) 4, the key receptor for lipopoiysaccharide (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 wildtype carriers for any of the cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, interferon-γ, 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.
AB - The heterozygous Asp299Gly mutation of the toll-like receptor (TLR) 4, the key receptor for lipopoiysaccharide (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 wildtype carriers for any of the cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, interferon-γ, 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.
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U2 - 10.1086/378095
DO - 10.1086/378095
M3 - Article
C2 - 12964127
AN - SCOPUS:0141840748
VL - 188
SP - 938
EP - 943
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 6
ER -