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Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines.
Clin Exp Immunol. 2003 Feb; 131(2):264-7.CE

Abstract

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.

Authors+Show Affiliations

Institute of Medical Chemistry and Biochemistry, Leopold Franzens University, Department of Internal Medicine, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12562386

Citation

Neurauter, G, et al. "Atorvastatin Suppresses Interferon-gamma -induced Neopterin Formation and Tryptophan Degradation in Human Peripheral Blood Mononuclear Cells and in Monocytic Cell Lines." Clinical and Experimental Immunology, vol. 131, no. 2, 2003, pp. 264-7.
Neurauter G, Wirleitner B, Laich A, et al. Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin Exp Immunol. 2003;131(2):264-7.
Neurauter, G., Wirleitner, B., Laich, A., Schennach, H., Weiss, G., & Fuchs, D. (2003). Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clinical and Experimental Immunology, 131(2), 264-7.
Neurauter G, et al. Atorvastatin Suppresses Interferon-gamma -induced Neopterin Formation and Tryptophan Degradation in Human Peripheral Blood Mononuclear Cells and in Monocytic Cell Lines. Clin Exp Immunol. 2003;131(2):264-7. PubMed PMID: 12562386.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. AU - Neurauter,G, AU - Wirleitner,B, AU - Laich,A, AU - Schennach,H, AU - Weiss,G, AU - Fuchs,D, PY - 2003/2/4/pubmed PY - 2003/4/8/medline PY - 2003/2/4/entrez SP - 264 EP - 7 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 131 IS - 2 N2 - 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. SN - 0009-9104 UR - https://www.unboundmedicine.com/medline/citation/12562386/Atorvastatin_suppresses_interferon_gamma__induced_neopterin_formation_and_tryptophan_degradation_in_human_peripheral_blood_mononuclear_cells_and_in_monocytic_cell_lines_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9104&date=2003&volume=131&issue=2&spage=264 DB - PRIME DP - Unbound Medicine ER -