The cytokine synthesis by heterozygous carriers of the Toll-like receptor 4 Asp299Gly polymorphism does not differ from that of wild type homozygotes.
Previous studies have found that heterozygosity for the A896G mutation of the endotoxin receptor TLR4 confers susceptibility to Gram-negative infections and septic shock. To evaluate the underlying mechanisms, we studied the association of the TLR4 polymorphism with endotoxin-induced cytokine synthesis in human whole blood. Monocyte CD14 density and monocyte count were also determined. Healthy individuals were genotyped by means of a real-time polymerase chain reaction. Plasma concentrations of TNF-alpha, IL-6, and IL-8 were measured by chemiluminescence. No significant differences in cytokine synthesis were observed between heterozygous individuals and homozygous carriers of the wild type allele. Our study suggests that heterozygosity for this TLR4 mutation is not a major factor determining the cytokine response to endotoxin.
Heesen
Michael
M
Department of Anesthesia, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, Netherlands. m.heesen@amc.uva.nl
Bloemeke
Brunhilde
B
Kunz
Dagmar
D
D019943:Amino Acid Substitution; D016207:Cytokines / Q000096:biosynthesis*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors