Differential Effects of the Anti-TNF-α Agents in Mediating Inhibition of LPS- and PHA-stimulated Cytokine Production in Whole Blood Cultures

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.

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Cytokine production by leukocytes of Papillon–Lefèvre syndrome patients in whole blood cultures

Clinical Oral Investigations ◽

10.1007/s00784-011-0532-0 ◽

2011 ◽

Vol 16 (2) ◽

pp. 591-597 ◽

Cited By ~ 2

Author(s):

Christian D. Sadik ◽

Barbara Noack ◽

Beate Schacher ◽

Josef Pfeilschifter ◽

Heiko Mühl ◽

...

Keyword(s):

Whole Blood ◽

Cytokine Production ◽

Blood Cultures

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Blood Cell In Vitro Cytokine Production in Response to Lipopolysaccharide Stimulation in a Healthy Population: Effects of Age, Sex, and Smoking

Cells ◽

10.3390/cells11010103 ◽

2021 ◽

Vol 11 (1) ◽

pp. 103

Author(s):

Lluis Rodas ◽

Sonia Martínez ◽

Aina Riera-Sampol ◽

Hannah J. Moir ◽

Pedro Tauler

Keyword(s):

Whole Blood ◽

Cytokine Production ◽

Culture Media ◽

Sex Change ◽

Healthy Population ◽

Statistical Regression ◽

Cross Sectional ◽

Tnf Α ◽

Age Change

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.

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Acute high-intensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00348.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. R529-R538 ◽

Cited By ~ 24

Author(s):

Cody Durrer ◽

Monique Francois ◽

Helena Neudorf ◽

Jonathan P. Little

Keyword(s):

Type 2 Diabetes ◽

Whole Blood ◽

Blood Cultures ◽

Toll Like Receptor ◽

Single Session ◽

Tnf Α ◽

Anti Inflammatory ◽

High Intensity Interval ◽

The Impact

Type 2 diabetes (T2D) is characterized by chronic low-grade inflammation that contributes to disease pathophysiology. Exercise has anti-inflammatory effects, but the impact of high-intensity interval training (HIIT) is not known. The purpose of this study was to determine the impact of a single session of HIIT on cellular, molecular, and circulating markers of inflammation in individuals with T2D. Participants with T2D ( n = 10) and healthy age-matched controls (HC; n = 9) completed an acute bout of HIIT (7 × 1 min at ~85% maximal aerobic power output, separated by 1 min of recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at 1 h of recovery (1-h Post). Inflammatory markers on leukocytes were measured by flow cytometry, and TNF-α was assessed in both LPS-stimulated whole blood cultures and plasma. A single session of HIIT had an overall anti-inflammatory effect, as evidenced by 1) significantly lower levels of Toll-like receptor (TLR) 2 surface protein expression on both classical and CD16+ monocytes assessed at Post and 1-h Post compared with Pre ( P < 0.05 for all); 2) significantly lower LPS-stimulated TNF-α release in whole blood cultures at 1-h Post ( P < 0.05 vs. Pre); and 3) significantly lower levels of plasma TNF-α at 1-h Post ( P < 0.05 vs. Pre). There were no differences between T2D and HC, except for a larger decrease in plasma TNF-α in HC vs. T2D (group × time interaction, P < 0.05). One session of low-volume HIIT has immunomodulatory effects and provides potential anti-inflammatory benefits to people with, and without, T2D.

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