Determination of tumour necrosis factor-α and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation

Linden, M.W. van der; Huizinga, Tom W J; Stoeken, Dirk-Jan; Sturk, Augueste; Westendorp, Rudi G.J.

doi:10.1016/s0022-1759(98)00108-2

Cited by 125 publications

(93 citation statements)

References 22 publications

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“…The whole blood cell culture method has proven to be reliable 11,19 and represents a more physiological situation than examination of isolated PBMC. 17 The variance between pairs in IL-10 production was nearly equal in the MZ and DZ group whereas the variance within pairs showed striking differences between the two groups ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

et al. 2002

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Interleukin-10 (IL-10) has a critical role in the regulation of immune responses. The relative contribution of genetic and environmental factors to IL-10 production is under debate. We performed a twin study in 246 monozygotic and dizygotic twins to assess the heritability of IL-10 production after LPS stimulation in whole blood. In addition, the influence of promoter single nucleotide polymorphisms (À1082, À819 and À592) on transcriptional activity and their binding to nuclear factors was studied in luciferase reporter gene and electrophoretic mobility shift assays. IL-10 production showed a genetic determination with a heritability of 0.5. Decreasing body mass index (BMI), smoking and female gender lead to decreased IL-10 production. In monocytes, the À1082A allele showed higher binding affinity to the transcription factor PU.1 resulting in decreased transcriptional activity of À1082A promoter haplotypes. Genetic determination of IL-10 secretion is probably lower than that previously reported. Fifty percent of the observed variability explained by genetic factors. Female individuals produce less IL-10 than male subjects. Environmental factors like smoking and decreasing BMI exert suppressing effects on IL-10 production. Although the À1082A allele shows higher binding affinity to the PU.1 transcription factor and lower transcriptional activity, this polymorphism probably explains only a small fraction of the observed heritability.

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Section: Resultsmentioning

confidence: 99%

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

et al. 2002

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“…1 Despite being a commonly used technique, limitations in using LPS stimulation of whole-blood exist. 31 Despite the ease of assaying whole blood and the minimal amount of tissue perturbation required compared with monocyte isolation, it is difficult to correct for differences in leukocyte count among individuals as well as the influence of various soluble factors, such as LBP and soluble CD14, which may modify endotoxin signaling. Our previous study, in which we adjusted for blood monocyte counts, provides reassurance that any differences in circulating monocyte numbers have little effect on our observations.…”

Section: Discussionmentioning

confidence: 99%

The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes

et al. 2004

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Toll-like receptor 4 (TLR-4) is required for detection of Gram negative bacterial infections by binding lipopolysaccharide (LPS) and for the initiation of inflammatory signaling. Recent studies have demonstrated that a nonsynonymous single-nucleotide polymorphism (Asp299Gly, A þ 896G) is associated with decreased endotoxin responsiveness and poor outcomes from sepsis. We show that human carriers of this polymorphism show no deficit in LPS induced peripheral blood mononuclear cell (PBMC) mitogen-activated protein kinase (MAPK) activity, no reduction in sensitivity to endotoxin, and variable differences in whole-blood inflammatory cytokine production. These results indicate that this mutation is not a primary determinant of human endotoxin sensitivity.

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“…The level of TNF production in healthy individuals shows wide and stable variation, with high and low producer phenotypes present in the population, 7,8 indicating a substantial genetic contribution to TNF regulation. In an important paper, Westendorp et al 9 showed that the levels of both TNF and IL-10 in firstdegree relatives of patients with meningococcal disease strongly determined the likelihood of patient survival.…”

Section: Introductionmentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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Determination of tumour necrosis factor-α and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation

Cited by 125 publications

References 22 publications

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes

Is there a future for TNF promoter polymorphisms?

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