Pravastatin down-regulates inflammatory mediators in human monocytes in vitro

There is experimental evidence that pravastatin, which is designed to inhibit the rate-limiting enzyme of cholesterol synthesis, can affect cell metabolism and proliferation. We therefore studied the effects of pravastatin on the generation of inflammatory mediators in non-stimulated and stimulated primary human monocytes in vitro. In our experimental model, pravastatin induced a dose-dependent inhibition of monocyte cholesterol synthesis (up to 67%), up-regulation of low density lipoprotein receptor mRNA (by about 35%) and reduction in intracellular cholesterol accumulation. In parallel, exposure of non-stimulated monocytes to various doses of pravastatin resulted in inhibition of monocyte chemoattractant protein-1 protein expression (up to 15-fold), reduction of tumour necrosis factor alpha (TNF-alpha) levels (up to 2.4-fold) and a total loss of metalloproteinase-9 activity in stimulated cells. Pravastatin at concentrations of 5, 100 and 500 muM caused an inhibition of TNF-alpha -induced cellular oxygen consumption from 2.4- to 5.5-fold. These data extend the findings of potential anti-inflammatory actions of statins and also suggest the possibility for pravastatin use in a broader spectrum of inflammatory situations. (C) 2000 Elsevier Science B.V. All rights reserved.