title: Increased circulating CC chemokine levels in the metabolic syndrome are reduced by low-dose atorvastatin treatment: evidence from a randomized controlled trial.
abstract: OBJECTIVE
  Central obesity and insulin resistance are key components of the metabolic syndrome, which is associated with an increased risk of cardiovascular disease. In obesity, CC chemokines, such as monocyte chemotactic protein-1 (MCP-1), macrophage inhibitory protein-1β (MIP-1β) and eotaxin-1 and their respective receptors, are critically involved in peripheral monocyte activation and adipose tissue infiltration. The aim of the current study was to examine whether low-dose atorvastatin (10 mg/d) treatment modulated serum levels of CC chemokines in metabolic syndrome subjects.
  
  
  METHODS
  Serum levels of MCP-1, eotaxin-1, MIP-1β, C reactive protein (CRP) and interleukin-6 (IL-6) were measured in lean control and metabolic syndrome subjects at baseline, and following a 6-week randomized placebo-controlled clinical trial of atorvastatin (10 mg/d). Peripheral CD14(+) monocytes were isolated and mRNA levels of MCP-1, MIP-1 β and CCR5 determined.
  
  
  RESULTS
  Serum MCP-1 (P = 0·02), eotaxin-1 (P = 0·02) and MIP-1β (P = 0·03), CRP (P < 0·001) and IL-6 (P = 0·006) were significantly increased in metabolic syndrome in comparison with lean controls. Furthermore, CD14(+) peripheral monocyte mRNA expression of the chemokine receptor, CCR5, of which MIP-1β and eotaxin-1 are ligands, was increased two-fold in the metabolic syndrome group (P = 0·03). In addition to the expected improvements in lipid profile, atorvastatin treatment significantly reduced circulating eotaxin-1 (P < 0·05), MIP-1β (P < 0·05) levels and CD14(+) peripheral monocyte CCR5 mRNA expression (P = 0·02).
  
  
  CONCLUSIONS
  These results support a model whereby atorvastatin treatment, by inhibiting CD14(+) monocyte CCR5 expression, may inhibit monocyte trafficking, reduce chronic inflammation and, thus, lower circulating levels of CC chemokines.
authors.affiliation: Clinical Biochemistry, Royal Victoria Hospital, Belfast, UK.
authors.forename: Brona V
authors.initials: BV
authors.lastname: Loughrey
authors.forename: Ann
authors.initials: A
authors.lastname: McGinty
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: David R
authors.initials: DR
authors.lastname: McCance
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Powell
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism; D054413:Chemokine CCL11 / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D054407:Chemokine CCL4 / Q000097:blood / Q000235:genetics; D019742:Chemokines, CC / Q000097:blood* / Q000235:genetics; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D019713:Receptors, CCR5 / Q000097:blood / Q000235:genetics
chemical_list: D000924:Anticholesteremic Agents; C515456:CCL11 protein, human; C111835:CCL2 protein, human; C066507:CCL4 protein, human; C584933:CCR5 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D019742:Chemokines, CC; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D011758:Pyrroles; D012333:RNA, Messenger; D019713:Receptors, CCR5; D002097:C-Reactive Protein; D000069059:Atorvastatin