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 microM 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.
Grip
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O
Department of Medicine, Division of Gastroenterology and Hepatology, Lund University, University Hospital MAS, S-20502, Malmö, Sweden. olof.grip@medforsk.mas.lu.se
Janciauskiene
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S
Lindgren
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S
D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D017931:DNA Primers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D008666:Metalloendopeptidases; D017035:Pravastatin