title: Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans.
abstract: The aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-alpha, interleukin (IL)-18, interferon (IFN)-gamma, IL-6 and IL-10 affect the cytokine response during a controlled low-grade inflammatory response in vivo. Two hundred healthy young male volunteers were genotyped, and cytokine levels were measured in response to a low-dose intravenous bolus of Escherichia coli endotoxin. No association was detected between SNPs (TLR-4299, TLR-4399, TNF-308, IL-18-137, IL-18-607, IFN-gamma+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-alpha, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-alpha, IL-6, IL-18 or IL-10 in healthy young men. Previous reports of a major heritability factor in the inflammatory response may be due to other target genes or effects in older age groups or women.
authors.affiliation: Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshiospitalet, Unviersity of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark. sarahtaudorf@dadlnet.dk
authors.forename: S
authors.initials: S
authors.lastname: Taudorf
authors.forename: K S
authors.initials: KS
authors.lastname: Krabbe
authors.forename: R M G
authors.initials: RM
authors.lastname: Berg
authors.forename: K
authors.initials: K
authors.lastname: Møller
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: H
authors.initials: H
authors.lastname: Bruunsgaard
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D019446:Endotoxemia / Q000235:genetics* / Q000276:immunology; D004731:Endotoxins / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D016207:Cytokines; D004731:Endotoxins; D007378:Interleukins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D007371:Interferon-gamma