Atorvastatin suppresses interferon‐γ‐induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines

• Published in: Clinical and experimental immunology Vol. 131; no. 2; pp. 264 - 267
• Main Authors: NEURAUTER, G., WIRLEITNER, B., LAICH, A., SCHENNACH, H., WEISS, G., FUCHS, D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2003; Blackwell; Oxford University Press; Blackwell Publishing Inc
• Subjects: Atorvastatin; Biological and medical sciences; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; General and cellular metabolism. Vitamins; Heptanoic Acids - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; IDO; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - pharmacology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Medical sciences; Monocytes - drug effects; Monocytes - metabolism; MonoMac6; neopterin; Neopterin - biosynthesis; Original; Pharmacology. Drug treatments; Pyrroles - pharmacology; statins; THP‐1; Tryptophan - metabolism; Human; IDO MonoMac6 neopterin statins THP-1; Immune response; Enzyme; Cytokine; Enzyme inhibitor; Tryptophan; Pharmacology; Statin derivative; Biological activity; Degradation; T-Lymphocyte; Production; Atorvastatin; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent; Gamma interferon; Macrophage
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2003.02021.x

SUMMARY Inhibitors of 3‐hydroxy‐3methylglutaryl‐co‐enzyme A (HMG‐CoA) reductase, so‐called statins, are used in medical practice because of their lipid‐lowering effect and to reduce the risk of coronary heart disease. Recent findings indicate that statins also have anti‐inflammatory properties and can modulate the immune response. In vitro, we investigated the effect of atorvastatin on the T cell/macrophage system in peripheral blood mononuclear cells (PBMC) and in the human monocytic cell lines THP‐1 and MonoMac6. We monitored neopterin production and tryptophan degradation in PBMC after treatment with 10 µm and 100 µm atorvastatin in the presence or absence of 100 U/ml IFN‐γ, 10 µg/ml phytohaemagglutinin (PHA) or 10 µg/ml concanavalin A (ConA) and in monocytic cell lines THP‐1 and MonoMac6 with or without stimulation with 100 U/ml IFN‐γ or 10 ng/ml to 1 µg/ml lipopolysaccharide (LPS). In stimulated PBMC 100 µm atorvastatin inhibited neopterin formation and tryptophan degradation completely, whereas 10 µm atorvastatin was only partially effective. Also in monocytic cell lines THP‐1 and MonoMac6, atorvastatin was able to suppress IFN‐γ‐ and LPS‐induced formation of neopterin and degradation of tryptophan. Our data from PBMC agree well with previous investigations that statins inhibit T cell activation within the cellular immune response. In addition we demonstrate that atorvastatin directly inhibits IFN‐γ‐mediated pathways in monocytic cells, suggesting that both immunoreactivity of T cells and of monocyte‐derived macrophages are down‐regulated by this statin.