Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans.
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.
Taudorf
S
S
Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshiospitalet, Unviersity of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark. sarahtaudorf@dadlnet.dk
Krabbe
K S
KS
Berg
R M G
RM
Møller
K
K
Pedersen
B K
BK
Bruunsgaard
H
H
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
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