Heart and Vessels

, Volume 26, Issue 6, pp 596–602 | Cite as

In patients with idiopathic venous thrombosis, interleukin-10 is decreased and related to endothelial dysfunction

Original Article


The aim of this study was to evaluate the levels of anti-inflammatory interleukin-10 and pro-inflammatory cytokines and their relationship to endothelial function in patients with idiopathic venous thrombosis. Forty-nine eligible patients of both sexes with idiopathic venous thrombosis and 48 matched control subjects were studied. Levels of inflammatory markers were determined. Endothelial function was evaluated by ultrasound measurement of the flow mediated dilatation (FMD) of the brachial artery. Compared to the control group, patients with idiopathic venous thrombosis had significantly lower levels of interleukin-10 1.81 pg/ml (1.53–2.21) versus 2.71 pg/ml (1.84–3.65), p < 0.001. Patients also had increased levels of pro-inflammatory cytokines: interleukin-6 2.37 pg/ml (1.59–4.09) versus 2.03 pg/ml (1.49–2.59), p = 0.025, interleukin-8 3.53 pg/ml (2.94–5.30) versus 2.25 pg/ml (1.77–2.90), p < 0.001. Furthermore, decreased FMD was observed in patients: 5.0% (3.9–6.9) versus 12.7% (10.8–15.6), p < 0.001. FMD was related to levels of interleukin-10 (r = 0.33, p = 0.001) and was inversely related to pro-inflammatory cytokines interleukin-6 (r = −0.34, p = 0.001) and interleukin-8 (r = −0.43, p < 0.001). Patients with idiopathic venous thrombosis have decreased levels of IL-10 and increased levels of pro-inflammatory cytokines. This imbalance indicates that in the stable phase of the disease, patients have an increased systemic inflammatory response. This inflammatory response could be the consequence of the disease, but most probably is involved in the pathogenesis of venous thrombosis.


Endothelial dysfunction Markers of inflammation Interleukins Venous thrombosis 


  1. 1.
    Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson FA Jr, Spencer FA (2003) Risk factors for venous thromboembolism. Circulation 107:I9–I16PubMedCrossRefGoogle Scholar
  3. 3.
    Conde I, Lopez JA (2005) Classification of venous thromboembolism (VTE). Role of acute inflammatory stress in venous thromboembolism. J Thromb Haemost 3:2573–2575PubMedCrossRefGoogle Scholar
  4. 4.
    Wakefield TW, Strieter RM, Prince MR, Downing LJ, Greenfield LJ (1997) Pathogenesis of venous thrombosis: a new insight. Cardiovasc Surg 5:6–15PubMedCrossRefGoogle Scholar
  5. 5.
    Sprague AH, Khalil RA (2009) Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 78:539–552PubMedCrossRefGoogle Scholar
  6. 6.
    Reitsma PH, Rosendaal FR (2004) Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia Study. J Thromb Haemost 2:619–622PubMedCrossRefGoogle Scholar
  7. 7.
    Downing LJ, Strieter RM, Kadell AM, Wilke CA, Austin JC, Hare BD, Burdick MD, Greenfield LJ, Wakefield TW (1998) IL-10 regulates thrombus-induced vein wall inflammation and thrombosis. J Immunol 161:1471–1476PubMedGoogle Scholar
  8. 8.
    Pradier O, Gerard C, Delvaux A, Lybin M, Abramowicz D, Capel P, Velu T, Goldman M (1993) Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide. Eur J Immunol 23:2700–2703PubMedCrossRefGoogle Scholar
  9. 9.
    Del Prete G, De Carli M, Lammel RM, D’Elios MM, Daniel KC, Giusti B, Abbate R, Romagnani S (1995) Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes. Blood 86:250–257PubMedGoogle Scholar
  10. 10.
    Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM (2000) Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 102:1000–1006PubMedGoogle Scholar
  11. 11.
    Bhagat K, Vallance P (1997) Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation 96:3042–3047PubMedGoogle Scholar
  12. 12.
    Migliacci R, Becattini C, Pesavento R, Davi G, Vedovati MC, Guglielmini G, Falcinelli E, Ciabattoni G, Dalla Valle F, Prandoni P, Agnelli G, Gresele P (2007) Endothelial dysfunction in patients with spontaneous venous thromboembolism. Haematologica 92:812–818PubMedCrossRefGoogle Scholar
  13. 13.
    Jezovnik MK, Poredos P, Stalc M (2010) Impairment of the vasodilatation capability of the brachial artery in patients with idiopathic venous thrombosis. J Atheroscler Thromb 17:1190–1198PubMedCrossRefGoogle Scholar
  14. 14.
    Fichtlscherer S, Breuer S, Heeschen C, Dimmeler S, Zeiher AM (2004) Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease. J Am Coll Cardiol 44:44–49PubMedCrossRefGoogle Scholar
  15. 15.
    Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265PubMedCrossRefGoogle Scholar
  16. 16.
    Celermajer DS (1998) Noninvasive detection of atherosclerosis. N Engl J Med 339:2014–2015PubMedCrossRefGoogle Scholar
  17. 17.
    Christiansen SC, Naess IA, Cannegieter SC, Hammerstrom J, Rosendaal FR, Reitsma PH (2006) Inflammatory cytokines as risk factors for a first venous thrombosis: a prospective population-based study. PLoS Med 3:e334PubMedCrossRefGoogle Scholar
  18. 18.
    Dosquet C, Weill D, Wautier JL (1995) Cytokines and thrombosis. J Cardiovasc Pharmacol 25(Suppl 2):S13–S19PubMedCrossRefGoogle Scholar
  19. 19.
    Chrysohoou C, Pitsavos C, Barbetseas J, Kotroyiannis I, Brili S, Vasiliadou K, Papadimitriou L, Stefanadis C (2009) Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study). Heart Vessels 24:22–26PubMedCrossRefGoogle Scholar
  20. 20.
    Derosa G, Ferrari I, D’Angelo A, Salvadeo SA, Fogari E, Gravina A, Mereu R, Palumbo I, Maffioli P, Randazzo S, Cicero AF (2009) Oral fat load effects on inflammation and endothelial stress markers in healthy subjects. Heart Vessels 24:204–210PubMedCrossRefGoogle Scholar
  21. 21.
    Bergman M, Djaldetti M, Salman H, Bessler H (2010) On the combined effect of statins and lycopene on cytokine production by human peripheral blood cells. Heart Vessels 25:426–431PubMedCrossRefGoogle Scholar
  22. 22.
    Roumen-Klappe EM, den Heijer M, van Uum SH, van der Ven-Jongekrijg J, van der Graaf F, Wollersheim H (2002) Inflammatory response in the acute phase of deep vein thrombosis. J Vasc Surg 35:701–706PubMedCrossRefGoogle Scholar
  23. 23.
    Proctor MC, Sullivan V, Zajkowski P, Wolk SW, Pomerantz RA, Wakefield TW, Greenfield LJ (2006) A role for interleukin-10 in the assessment of venous thromboembolism risk in injured patients. J Trauma 60:147–151PubMedCrossRefGoogle Scholar
  24. 24.
    Poredos P (2004) Involvement of endothelial dysfunction in atherogenesis. In: Clark JV (ed) Focus on atherosclerosis research. Nova Science Publishers, Inc, Hauppauge, NY, USA, pp 165–183Google Scholar
  25. 25.
    Taddei S, Salvetti A (2002) Endothelial dysfunction in essential hypertension: clinical implications. J Hypertens 20:1671–1674PubMedCrossRefGoogle Scholar
  26. 26.
    Poredos P, Kek A (2000) Relation of blunted dilation of the brachial artery in insulin-dependent diabetes mellitus to microalbuminuria. Am J Cardiol 86:364–367PubMedCrossRefGoogle Scholar
  27. 27.
    Commins S, Steinke JW, Borish L (2008) The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol 121:1108–1111PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Department of Vascular DiseaseUniversity Medical Centre LjubljanaLjubljanaSlovenia

Personalised recommendations