title: Reduction of monocyte chemoattractant protein 1 and macrophage migration inhibitory factor by a polyphenol-rich extract in subjects with clustered cardiometabolic risk factors.
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.
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Lysette N
authors: LN
authors: Broekhuizen
authors: Diederik F
authors: DF
authors: van Wijk
authors: Hans
authors: H
authors: Vink
authors: A
authors: A
authors: Stalmach
authors: A
authors: A
authors: Crozier
authors: B A
authors: BA
authors: Hutten
authors: John J P
authors: JJ
authors: Kastelein
authors: Paul G
authors: PG
authors: Hugenholtz
authors: Wolfgang
authors: W
authors: Koenig
authors: Erik S G
authors: ES
authors: Stroes
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood*; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control*; D008875:Middle Aged; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D010936:Plant Extracts; D059808:Polyphenols