3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins) exhibit a wide variety of anti‐atherogenic effects that may be independent of their property to lower plasma cholesterol.

In order to systematically investigate these effects at a cellular level, we investigated gene expression in phorbol myristate acetate (PMA)‐activated and non‐activated human THP‐1 monocytes in response to statins using cDNA arrays.

Of 588 genes tested, 26 were differentially expressed in the presence of statins. A marked reduction was found for the chemokine macrophage inflammatory protein‐1α (MIP‐1α). The decrease in MIP‐1α mRNA expression after incubation with statins was confirmed by quantitative reverse transcription–polymerase chain reaction in THP‐1 monocytes and human freshly isolated monocytes. Macrophage inflammatory protein‐1α protein in THP‐1 monocytes was reduced from 377 to 299 and 305 pg/mL by 0.1 µmol/L simvastatin and 0.01 µmol/L cerivastatin, respectively. The reduction in MIP‐1α expression by statins was due, at least in part, to transcriptional inhibition of MIP‐1α promoter activity.

The CC receptor ligand MIP‐1α is a chemokine that has been implicated in atherosclerotic lesion formation. The present findings suggest that statin‐mediated immunomodulation by inhibiting MIP‐1α could contribute to the beneficial effects of statin therapy independent of lowering plasma cholesterol.