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Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study.

van Erk MJ, Wopereis S, Rubingh C, van Vliet T, Verheij E, Cnubben NH, Pedersen TL, Newman JW, Smilde AK, van der Greef J, Hendriks HF, van Ommen B - BMC Med Genomics (2010)

Bottom Line: Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes.Reducing inflammatory responses may reduce these risks.Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET.

View Article: PubMed Central - HTML - PubMed

Affiliation: TNO Quality of Life, PO Box 360, 3700 AJ Zeist, the Netherlands. marjan.vanerk@tno.nl

ABSTRACT

Background: Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy.

Methods: To address this limitation, we used an integrative omics approach to characterize modulation of inflammation in overweight men during an intervention with the non-steroidal anti-inflammatory drug diclofenac. Measured parameters included 80 plasma proteins, >300 plasma metabolites (lipids, free fatty acids, oxylipids and polar compounds) and an array of peripheral blood mononuclear cells (PBMC) gene expression products. These measures were submitted to multivariate and correlation analysis and were used for construction of biological response networks.

Results: A panel of genes, proteins and metabolites, including PGE2 and TNF-alpha, were identified that describe a diclofenac-response network (68 genes in PBMC, 1 plasma protein and 4 plasma metabolites). Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET.

Conclusion: In this study the integrated analysis of a wide range of parameters allowed the development of a network of markers responding to inflammatory modulation, thereby providing insight into the complex process of inflammation and ways to assess changes in inflammatory status associated with obesity.

Trial registration: The study is registered as NCT00221052 in clinicaltrials.gov database.

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Related in: MedlinePlus

PGE2 levels before (day0) and after (day9) supplementation with placebo and diclofenac. The PGE2 response was significantly different for diclofenac compared to placebo (ANOVA, treatment * time interaction P < 0.05). In the diclofenac group, the difference in PGE2 level between day 9 and day 0 was significant (p-value = 0.0469).
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Figure 1: PGE2 levels before (day0) and after (day9) supplementation with placebo and diclofenac. The PGE2 response was significantly different for diclofenac compared to placebo (ANOVA, treatment * time interaction P < 0.05). In the diclofenac group, the difference in PGE2 level between day 9 and day 0 was significant (p-value = 0.0469).

Mentions: As expected, diclofenac treatment decreased PGE2 levels (48.9 ± 10.6 pg/mL (mean ± stdev) at day 9 compared to 55.3 ± 11.9 pg/mL at day0, p = 0.047), as displayed in figure 1. In contrast, CRP levels were significantly reduced in the placebo group (2.05 ± 2.30 μg/mL (mean ± stdev) at day 9 compared to 4.03 ± 3.34 μg/mL at day0, p = 0.0062), but not in the diclofenac group. As illustrated in figure 2, four subjects in the placebo group exhibited elevated CRP levels (>5 μg/mL) at day 0. The CRP levels in three of these subjects dropped below 2 μg/mL at day 9, resulting in a 3.6 to 8 fold reduction in CRP levels at day 9 compared to day 0.


Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study.

van Erk MJ, Wopereis S, Rubingh C, van Vliet T, Verheij E, Cnubben NH, Pedersen TL, Newman JW, Smilde AK, van der Greef J, Hendriks HF, van Ommen B - BMC Med Genomics (2010)

PGE2 levels before (day0) and after (day9) supplementation with placebo and diclofenac. The PGE2 response was significantly different for diclofenac compared to placebo (ANOVA, treatment * time interaction P < 0.05). In the diclofenac group, the difference in PGE2 level between day 9 and day 0 was significant (p-value = 0.0469).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837611&req=5

Figure 1: PGE2 levels before (day0) and after (day9) supplementation with placebo and diclofenac. The PGE2 response was significantly different for diclofenac compared to placebo (ANOVA, treatment * time interaction P < 0.05). In the diclofenac group, the difference in PGE2 level between day 9 and day 0 was significant (p-value = 0.0469).
Mentions: As expected, diclofenac treatment decreased PGE2 levels (48.9 ± 10.6 pg/mL (mean ± stdev) at day 9 compared to 55.3 ± 11.9 pg/mL at day0, p = 0.047), as displayed in figure 1. In contrast, CRP levels were significantly reduced in the placebo group (2.05 ± 2.30 μg/mL (mean ± stdev) at day 9 compared to 4.03 ± 3.34 μg/mL at day0, p = 0.0062), but not in the diclofenac group. As illustrated in figure 2, four subjects in the placebo group exhibited elevated CRP levels (>5 μg/mL) at day 0. The CRP levels in three of these subjects dropped below 2 μg/mL at day 9, resulting in a 3.6 to 8 fold reduction in CRP levels at day 9 compared to day 0.

Bottom Line: Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes.Reducing inflammatory responses may reduce these risks.Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET.

View Article: PubMed Central - HTML - PubMed

Affiliation: TNO Quality of Life, PO Box 360, 3700 AJ Zeist, the Netherlands. marjan.vanerk@tno.nl

ABSTRACT

Background: Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy.

Methods: To address this limitation, we used an integrative omics approach to characterize modulation of inflammation in overweight men during an intervention with the non-steroidal anti-inflammatory drug diclofenac. Measured parameters included 80 plasma proteins, >300 plasma metabolites (lipids, free fatty acids, oxylipids and polar compounds) and an array of peripheral blood mononuclear cells (PBMC) gene expression products. These measures were submitted to multivariate and correlation analysis and were used for construction of biological response networks.

Results: A panel of genes, proteins and metabolites, including PGE2 and TNF-alpha, were identified that describe a diclofenac-response network (68 genes in PBMC, 1 plasma protein and 4 plasma metabolites). Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET.

Conclusion: In this study the integrated analysis of a wide range of parameters allowed the development of a network of markers responding to inflammatory modulation, thereby providing insight into the complex process of inflammation and ways to assess changes in inflammatory status associated with obesity.

Trial registration: The study is registered as NCT00221052 in clinicaltrials.gov database.

Show MeSH
Related in: MedlinePlus