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Reduction of monocyte chemoattractant protein 1 and macrophage migration inhibitory factor by a polyphenol-rich extract in subjects with clustered cardiometabolic risk factors

  • Lysette N. Broekhuizen (a1), Diederik F. van Wijk (a1), Hans Vink (a2), A. Stalmach (a3), A. Crozier (a3), B. A. Hutten (a1), John J. P. Kastelein (a1), Paul G. Hugenholtz (a4), Wolfgang Koenig (a5) and Erik S. G. Stroes (a1)...

Abstract

Inflammation is a hallmark of the metabolic syndrome, which also contributes to a pro-atherogenic state. NF-κB activation, a critical step in regulating inflammatory reactions, can be inhibited by polyphenol (PF) extracts, at least in vitro. In the present study, we set out to study whether a PF-rich extract could attenuate the chronic inflammatory state and/or an acute immune response in vivo in subjects with clustered metabolic risk factors. A commercially available, PF-rich extract (500 mg daily) or placebo was administered for 4 weeks to thirty-four subjects with two or more metabolic risk factors using a randomised, double-blind, cross-over design. During the final study visit, an acute inflammatory challenge (lipopolysaccharide (LPS) 1 ng/kg body weight) was administered to a random subgroup of subjects (PF-rich extract (n 12) and placebo (n 12)). The PF-rich extract modestly reduced the inflammatory chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage migration inhibitory factor (MIF) (MCP-1 − 6·5 % (PF, median 116 (interquartile range 97–136) pg/ml v. placebo, median 124 (interquartile range 105–153) pg/ml; P < 0·05); MIF − 10·8 % (PF, median 2512 (interquartile range 1898–3972) pg/ml v. placebo, median 2814·5 (interquartile range 2296–3852) pg/ml; P < 0·05); however, other measured markers of inflammation and cardiometabolic disease, such as C-reactive protein, IL-6, HDL-cholesterol, adiponectin and oxidised LDL, remained unaffected. Following the LPS challenge, we found a statistically significant 48 % reduction of MCP-1 production in the PF-rich extract group (n 12) v. placebo (n 12) over 6 h (PF 766 (sd 155) v. placebo 1466 (sd 989) ng/ml; P < 0·05, area under the curve). In conclusion, short-term oral administration of the PF-rich extract caused a modest anti-inflammatory effect in subjects with clustered metabolic risk factors. Further dose-ranging studies are needed to evaluate whether and to what extent PF-rich extracts can be used to reduce the pro-inflammatory state in subjects with metabolic diseases at increased cardiovascular risk.

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Corresponding author

*Corresponding author: E. S. G. Stroes, fax +31 20 56 69343, email e.s.stroes@amc.uva.nl

References

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