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Increased circulating CC chemokine levels in the metabolic syndrome are reduced by low‐dose atorvastatin treatment: evidence from a randomized controlled trial
Author(s) -
Loughrey Brona V.,
McGinty Ann,
Young Ian S.,
McCance David R.,
Powell Lesley A.
Publication year - 2013
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12113
Subject(s) - eotaxin , medicine , endocrinology , metabolic syndrome , chemokine , atorvastatin , cd14 , monocyte , macrophage inflammatory protein , adipose tissue , immunology , inflammation , receptor , diabetes mellitus
Summary 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. Materials and 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 CD 14 + monocytes were isolated and mRNA levels of MCP ‐1, MIP ‐1 β and CCR 5 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, CCR 5, 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 CD 14 + peripheral monocyte CCR 5 m RNA expression ( P = 0·02). Conclusion These results support a model whereby atorvastatin treatment, by inhibiting CD 14 + monocyte CCR 5 expression, may inhibit monocyte trafficking, reduce chronic inflammation and, thus, lower circulating levels of CC chemokines.