Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines.
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 micro m and 100 micro m atorvastatin in the presence or absence of 100 U/ml IFN-gamma, 10 micro g/ml phytohaemagglutinin (PHA) or 10 micro g/ml concanavalin A (ConA) and in monocytic cell lines THP-1 and MonoMac6 with or without stimulation with 100 U/ml IFN-gamma or 10 ng/ml to 1 micro g/ml lipopolysaccharide (LPS). In stimulated PBMC 100 micro m atorvastatin inhibited neopterin formation and tryptophan degradation completely, whereas 10 micro m atorvastatin was only partially effective. Also in monocytic cell lines THP-1 and MonoMac6, atorvastatin was able to suppress IFN-gamma- 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-gamma-mediated pathways in monocytic cells, suggesting that both immunoreactivity of T cells and of monocyte-derived macrophages are down-regulated by this statin.
Neurauter
G
G
Institute of Medical Chemistry and Biochemistry, Leopold Franzens University, Department of Internal Medicine, Innsbruck, Austria.
Wirleitner
B
B
Laich
A
A
Schennach
H
H
Weiss
G
G
Fuchs
D
D
D000069059:Atorvastatin; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019798:Neopterin / Q000096:biosynthesis*; D011758:Pyrroles / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D000069059:Atorvastatin