title: Heterozygous toll-like receptor 4 polymorphism does not influence lipopolysaccharide-induced cytokine release in human whole blood.
abstract: 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.
authors.affiliation: Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
authors.forename: Nicolas W J
authors.initials: NW
authors.lastname: Schröder
authors.forename: Katja
authors.initials: K
authors.lastname: Gueinzius
authors.forename: Stephanie
authors.initials: S
authors.lastname: Traub
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Graf
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
authors.forename: Corinna
authors.initials: C
authors.lastname: Hermann
mesh_terms: 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
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors