scholarly journals SNP may modify the effect of vitamin A supplementation at birth on cytokine production in a whole blood culture assay

2011 ◽  
Vol 107 (5) ◽  
pp. 615-620 ◽  
Author(s):  
Mathias Jul Jørgensen ◽  
Ane Bærent Fisker ◽  
Christian Erikstrup ◽  
Mogens H. Claesson ◽  
Christine Stabell Benn

Within a neonatal vitamin A supplementation (VAS) trial, we investigated the effect of VAS on TNF-α, IL-10, IL-5 and IL-13 production after lipopolysaccharide, purified protein derivative (PPD) of Mycobacterium tuberculosis and phytohaemagglutinin stimulation using a whole blood culture protocol. We found that VAS recipients had lower unstimulated TNF-α concentrations than placebo recipients. In the present paper, we investigated whether the SNP TNF-α − 308, TNF-α − 238, IL-10 − 592, IL-10 − 1082 and toll-like receptor 4 (TLR4)+896 modified the effect of VAS on cytokine production. DNA and cytokine concentrations were available from 291 children. We found a significant interaction between TNF-α − 308 genotype and VAS for the unstimulated TNF-α production (Pinteraction = 0·04); among G homozygotes, TNF-α concentrations were significantly lower after VAS compared with placebo, whereas for A carriers, VAS did not appear to have any effect. For TNF-α − 238, there was a tendency towards an increase in PPD-stimulated TNF-α production after VAS for the G homozygotes, but the opposite tendency for A allele carriers (Pinteraction = 0·07). Stratification by sex revealed a significant VAS–genotype interaction for boys for TNF-α − 238. There was a borderline-significant three-way interaction (P = 0·05) between sex, VAS and TLR4+896 genotype. Although the present study had very limited representation of the genetic variation with potential for modification of the response to VAS, it adds to the efforts of untangling the diverse effects and impact of VAS.

2010 ◽  
Vol 24 (6) ◽  
pp. 901-907 ◽  
Author(s):  
Shigehiro Shibata ◽  
Gaku Takahashi ◽  
Nobuki Shioya ◽  
Katsuya Inada ◽  
Shigeatsu Endo

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 103
Author(s):  
Lluis Rodas ◽  
Sonia Martínez ◽  
Aina Riera-Sampol ◽  
Hannah J. Moir ◽  
Pedro Tauler

Immune system functionality has been commonly assessed by a whole-blood or isolated-cell stimulation assay. The aim of this study was to determine whether cytokine production in whole-blood-stimulated samples is influenced by age, sex, and smoking. A descriptive cross-sectional study in 253 healthy participants aged 18–55 years was conducted. Whole blood samples were stimulated for 24 h with LPS and concentrations of IL-6, IL-10, and TNF-α were determined in the culture media. Among parameters considered, statistical regression analysis indicated that smoking (change in R2 = 0.064, p < 0.001) and sex (change in R2 = 0.070, p < 0.001) were the main predictors for IL-10 production, with higher values for women and non-smokers. Age was also found to be a significant predictor (change in R2 = 0.021, p < 0.001), with higher values for younger ages. Age (change in R2 = 0.089, p = 0.013) and smoking (change in R2 = 0.037, p = 0.002) were found to be negative predictors for IL-6 production. Regarding TNF-α-stimulated production, age (change in R2 = 0.029, p = 0.009) and smoking (change in R2 = 0.022, p = 0.022) were found to be negative predictors. Furthermore, sex (change in R2 = 0.016, p = 0.045) was found to be a significant predictor, with lower values for women. In conclusion, sex, age, and smoking were found to be independent determinants of stimulated cytokine production. While female sex is associated with higher IL-10 and lower TNF-α production, aging and smoking are associated with lower IL-6, IL-10, and TNF-α production.


Maturitas ◽  
1997 ◽  
Vol 26 (1) ◽  
pp. 63-71 ◽  
Author(s):  
S.X. Zheng ◽  
Y. Vrindts ◽  
M. Lopez ◽  
D. De Groote ◽  
P.F. Zangerle ◽  
...  

2012 ◽  
Vol 109 (3) ◽  
pp. 467-477 ◽  
Author(s):  
Mathias J. Jørgensen ◽  
Ane B. Fisker ◽  
Erliyani Sartono ◽  
Andreas Andersen ◽  
Christian Erikstrup ◽  
...  

Vitamin A supplementation (VAS) at birth was not associated with improved survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a negative sex-differential effect, which became evident after diphtheria–tetanus–pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at birth was associated with two-fold higher mortality than placebo. The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the randomised trial. Guided by the mortality results, we further explored whether VAS had a differential effect according to sex and DTP status. At 6 weeks after randomisation and supplementation, we measured differential leucocyte counts and TNF-α, interferon-γ, IL-10, IL-13 and IL-5 production in a whole-blood culture assay. A total of 471 children were included. VAS compared with placebo at birth was associated with a higher proportion of monocytes (relative risk ratio 1·26, 95 % CI 1·07, 1·49, P= 0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95 % CI, 0·37, 0·78, P= 0·001). Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP, resulting in significant three-way interactions between VAS, sex and DTP vaccination status (P= 0·03 and P= 0·04, respectively) for spontaneous TNF-α and IL-10 production. The results substantiate the potential role of VAS as an immunomodulatory intervention, which has different effects depending on concomitant health interventions and the sex of the recipient.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Cheng-Shiun He ◽  
William D. Fraser ◽  
Michael Gleeson

Aim. Our aims were to determine the influence of plasma total 25-hydroxy vitamin D (25(OH)D) status on the plasma cytokine concentrations in athletes and the in vitro effects of different doses of 1, 25 dihydroxyvitamin D3 (1, 25(OH)2D3) on multiantigen stimulated cytokine production by whole blood and peripheral blood mononuclear cell (PBMC) cultures. Methods. Plasma samples from 43 athletes with high and low levels of 25(OH)D were assayed for the concentrations of cytokines. The whole blood samples and PBMCs from healthy subjects were incubated in vitro with a multi-antigen vaccine and different doses of added 1, 25(OH)2D3. The circulating cytokines and stimulated whole blood and PBMC culture production of cytokines were determined using a biochip assay. Results. The circulating interleukin-(IL-)10 and interferon-(IFN-) γ concentrations were significantly higher in the vitamin D sufficient athletes. Furthermore, the production of tumour necrosis factor-(TNF-) α, IL-6, IFN-γ, IL-2, and IL-10 by whole blood culture was significantly inhibited by 1, 25(OH)2D3 concentrations of 1000 pmol/L or 10000 pmol/L. Conclusions. We found that the influence of vitamin D on circulating cytokines might be different in athletes compared with nonathletes and cytokines production by whole blood culture was not influenced by 1, 25(OH)2D3 in concentrations within the normal healthy range.


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