Serum neopterin is not increased in obese juveniles

Harald Mangge, Florian Freytag, Gunter Almer, Daniel Weghuber, Carmen Bauer-Denk, Dietmar Fuchs, Harald Mangge, Florian Freytag, Gunter Almer, Daniel Weghuber, Carmen Bauer-Denk, Dietmar Fuchs

Abstract

Objective. Cardiovascular disease is associated with inflammation and immune activation, concentrations of immune activation markers like neopterin predict outcome in adults. Methods. Serum neopterin concentrations and early metabolic and pre-atherosclerotic symptoms were analyzed in 295 obese juveniles and 101 normal weight controls of similar age. Additionally, the influence of a 12 months weight reduction program on neopterin levels was investigated in 31 obese juveniles. Results. Intima-media thickness of common carotid arteries (IMT) and the concentrations of C-reactive protein (CRP) were increased in the obese juveniles (P < .001). Also triglycerides, oxidized LDL, fasted insulin levels, HOMA-index, leptin, liver transaminases and uric acid were increased compared to the controls. However, serum neopterin was decreased in the obese versus non-obese juveniles (P < .03). The intervention consisting of regular sports, nutritional devices, and a psychologic attendance led after 12 months to an increase of neopterin concentration (P < .05; paired test). Conclusions. Neopterin concentrations in juvenile obesity behaved considerably different from what was demonstrated in adults, levels did not correlate with metabolic and pre-atherosclerotic symptoms found in early phases although early vascular burden and chronic low grade inflammation was indicated by increased IMT and CRP. Neopterin concentrations increased after a 12 months intervention program.

Figures

Figure 1
Figure 1
Serum concentrations of neopterin and C-reactive protein in obese and nonobese adolescents. Neopterin concentrations are given as mean values (boxes) and S.E.M. (bars) and because of nonnormal distribution C-reactive protein is given as medians (boxes) and 25–75th percentiles (bars).

References

    1. Hansson GK. Mechanisms of disease: inflammation, atherosclerosis, and coronary artery disease. The New England Journal of Medicine. 2005;352(16):1685–1626.
    1. Vonhof S, Brost B, Stille-Siegener M, Grumbach IM, Kreuzer H, Figulla HR. Monocyte activation in congestive heart failure due to coronary artery disease and idiopathic dilated cardiomyopathy. International Journal of Cardiology. 1998;63(3):237–244.
    1. Tatzber F, Rabl H, Koriska K, et al. Elevated serum neopterin levels in atherosclerosis. Atherosclerosis. 1991;89(2-3):203–208.
    1. Weiss G, Willeit J, Kiechl S, et al. Increased concentrations of neopterin in carotid atherosclerosis. Atherosclerosis. 1994;106(2):263–271.
    1. Schumacher M, Halwachs G, Tatzber F, et al. Increased neopterin in patients with chronic and acute coronary syndromes. Journal of the American College of Cardiology. 1997;30(3):703–707.
    1. Gurfinkel EP, Scirica BM, Bozovich G, Macchia A, Manos E, Mautner B. Serum neopterin levels and the angiographic extent of coronary arterial narrowing in unstable angina pectoris and in non-Q-wave acute myocardial infarction. American Journal of Cardiology. 1999;83(4):515–518.
    1. Kiechl S, Lorenz E, Reindl M, et al. Toll-like receptor 4 polymorphisms and atherogenesis. The New England Journal of Medicine. 2002;347(3):185–192.
    1. Zouridakis E, Avanzas P, Arroyo-Espliguero R, Fredericks S, Kaski JC. Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris. Circulation. 2004;110(13):1747–1753.
    1. Avanzas P, Arroyo-Espliguero R, Quiles J, Roy D, Kaski JC. Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris. European Heart Journal. 2005;26(5):457–463.
    1. Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez M. Usefulness of neopterin levels and left ventricular function for risk assessment in survivors of acute myocardial infarction. International Journal of Cardiology. 2006;111(2):318–320.
    1. Johnston DT, Gagos M, Raio N, et al. Alterations in serum neopterin correlate with thrombolysis in myocardial infarction risk scores in acute coronary syndromes. Coronary Artery Disease. 2006;17(6):511–516.
    1. Ray KK, Morrow DA, Sabatine MS, et al. Long-term prognostic value of neopterin: a novel marker of monocyte activation in patients with acute coronary syndrome. Circulation. 2007;115(24):3071–3078.
    1. Adachi T, Naruko T, Itoh A, et al. Neopterin is associated with plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Heart. 2007;93(12):1537–1541.
    1. Kaski JC, Consuegra-Sanchez L, Fernandez-Berges DJ, et al. Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome. Atherosclerosis. 2008;201(1):176–183.
    1. Alber HF, Duftner C, Wanitschek M, et al. Neopterin, CD4+CD28− lymphocytes and the extent and severity of coronary artery disease. International Journal of Cardiology. 2009;135(1):27–35.
    1. Videm V, Wiseth R, Gunnes S, Madsen HO, Garred P. Multiple inflammatory markers in patients with significant coronary artery disease. International Journal of Cardiology. 2007;118(1):81–87.
    1. Grammer TB, Fuchs D, Boehm BO, Winkelmann BR, Maerz W. Neopterin as a predictor of total and cardiovascular mortality in individuals undergoing angiography in the Ludwigshafen Risk and Cardiovascular Health study. Clinical Chemistry. 2009;55(6):1135–1146.
    1. Vengen IT, Dale AC, Wiseth R, Midthjell K, Videm V. Neopterin predicts the risk for fatal ischemic heart disease in type 2 diabetes mellitus. Long-term follow-up of the HUNT 1 study. Atherosclerosis. 2009;207(1):239–244.
    1. Huber C, Batchelor JR, Fuchs D. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. Journal of Experimental Medicine. 1984;160(1):310–316.
    1. Wirleitner B, Reider D, Ebner S, et al. Monocyte-derived dendritic cells release neopterin. Journal of Leukocyte Biology. 2002;72(6):1148–1153.
    1. Murr C, Widner B, Wirleitner B, Fuchs D. Neopterin as a marker for immune system activation. Current Drug Metabolism. 2002;3(2):175–187.
    1. Fuchs D, Weiss G, Reibnegger G, Wachter H. The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Critical Reviews in Clinical Laboratory Sciences. 1992;29(3-4):307–341.
    1. Murr C, Bergant A, Widschwendter M, Heim K, Schröcksnadel H, Fuchs D. Neopterin is an independent prognostic variable in females with breast cancer. Clinical Chemistry. 1999;45(11):1998–2004.
    1. Reibnegger G, Aichberger C, Fuchs D, et al. Posttransplant neopterin excretion in renal allograft recipients—a reliable diagnostic aid for acute rejection and a predictive marker of long-term graft survival. Transplantation. 1991;52(1):58–63.
    1. Mangge H, Schauenstein K, Stroedter L, Griesl A, Maerz W, Borkenstein M. Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis. Experimental and Clinical Endocrinology and Diabetes. 2004;112(7):378–382.
    1. Pilz S, Horejsi R, Möller R, et al. Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. Journal of Clinical Endocrinology and Metabolism. 2005;90(8):4792–4796.
    1. Mangge H, Almer G, Haj-Yahya S, et al. Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis. 2009;203(1):277–283.
    1. Ledochowski M, Murr C, Widner B, Fuchs D. Association between insulin resistance, body mass and neopterin concentrations. Clinica Chimica Acta. 1999;282(1-2):115–123.
    1. Kiechl S, Willeit J. The natural course of atherosclerosis: part II: vascular remodeling. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19(6):1491–1498.
    1. Moeller R, Horejsi R, Pilz S, et al. Evaluation of risk profiles by subcutaneous adipose tissue topography in obese juveniles. Obesity. 2007;15(5):1319–1324.
    1. Winkelmann BR, März W, Boehm BO, et al. Rationale and design of the LURIC study—a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics. 2001;2(supplement 1):S1–S73.
    1. van Haelst PL, Liem A, van Boven AJ, et al. Usefulness of elevated neopterin and C-reactive protein levels in predicting cardiovascular events in patients with non-Q-wave myocardial infarction. American Journal of Cardiology. 2003;92(10):1201–1203.
    1. Cirillo P, Pacileo M, De Rosa S, et al. Neopterin induces pro-atherothrombotic phenotype in human coronary endothelial cells. Journal of Thrombosis and Haemostasis. 2006;4(10):2248–2255.
    1. Auer J, Berent R, Laßnig E, Eber B. Serum neopterin and activity of coronary artery disease. Heart Disease. 2001;3(5):297–301.
    1. Hoffmann G, Schobersberger W, Frede S, et al. Neopterin activates transcription factor nuclear factor-κB in vascular smooth muscle cells. FEBS Letters. 1996;391(1-2):181–184.
    1. Fuchs D, Avanzas P, Arroyo-Espliguero R, Jenny M, Consuegra-Sanchez L, Kaski JC. The role of neopterin in atherogenesis and cardiovascular risk assessment. Current Medicinal Chemistry. 2009;16(35):4644–4653.
    1. Weiss G, Murr C, Zoller H, et al. Modulation of neopterin formation and tryptophan degradation by Th1- and Th2-derived cytokines in human monocytic cells. Clinical and Experimental Immunology. 1999;116(3):435–440.
    1. Mayersbach P, Fuchs D, Schennach H. Performance of a fully automated quantitative neopterin measurement assay in a routine voluntary blood donation setting. Clinical Chemistry and Laboratory Medicine. 2010;48(3):373–377.
    1. Jenny M, Klieber M, Zaknun D, et al. In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors. Inflammation Research. In press.
    1. Sprenger H, Jacobs C, Nain M, et al. Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. Clinical Immunology and Immunopathology. 1992;63(2):188–195.
    1. Tilz GP, Domej W, Diez-Ruiz A, et al. Increased immune activation during and after physical excercise. Immunobiology. 1993;188(1-2):194–202.
    1. Ristow M, Zarse K, Oberbach A, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(21):8665–8670.
    1. Sun J, Sukhova GK, Wolters PJ, et al. Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nature Medicine. 2007;13(6):719–724.

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