, Volume 36, Issue 6, pp 1195–1200 | Cite as

Expression of Pro-Inflammatory Cytokines and the Risk of Intracranial Aneurysm

  • Hai-Feng Zhang
  • Ming-Guang Zhao
  • Guo-Biao Liang
  • Zhen-Quan Song
  • Zhi-Qing Li


Intracranial aneurysm (IA) lingers as a potentially devastating clinical problem, in which inflammation acts as a critical contributor to the pathogenesis of this disease. Cytokines play a major role in regulating inflammation. The aim of this study was to gain insight in the inflammatory response in IA by assessing plasma cytokine profiles. Plasma levels of 10 cytokines were quantified by multiplex protein arrays in 66 patients with IA and 78 healthy controls. Results showed that plasma level of interleukin 1 beta (IL-1β) was 2.4-fold higher in patients than in controls (p < 0.05). The level of monocyte chemoattractant protein-1 (MCP-1) was 2.8-fold higher in patient than in controls (p < 0.01). The level of tumor necrosis factor-alpha (TNF-α) was 2.1-fold higher in cases than in controls (p < 0.001). When comparing the expression of cytokines in IA patients with different characteristics, cases with ruptured aneurysm revealed increased level of MCP-1 than those with unruptured aneurysm (p < 0.05), whereas cases with multiple numbers of aneurysms demonstrated higher levels of MCP-1 and TNF-α than those with single aneurysm (p < 0.05 and p < 0.05, respectively). These data indicated that IL-1β, MCP-1, and TNF-α were associated with increased risk of IA and may affect the development of this disease.


cytokines inflammation intracranial aneurysm 


  1. 1.
    Juvela, S. 2011. Prevalence of and risk factors for intracranial aneurysms. Lancet Neurology 10: 595–597.PubMedCrossRefGoogle Scholar
  2. 2.
    Wermer, M.J., I.C. van der Schaaf, A. Algra, and G.J. Rinkel. 2007. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke 38: 1404–1410.PubMedCrossRefGoogle Scholar
  3. 3.
    Wiebers, D.O., J.P. Whisnant, J. Huston 3rd, I. Meissner, R.D. Brown Jr., D.G. Piepgras, et al. 2003. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362: 103–110.PubMedCrossRefGoogle Scholar
  4. 4.
    Nieuwkamp, D.J., L.E. Setz, A. Algra, F.H. Linn, N.K. de Rooij, and G.J. Rinkel. 2009. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurology 8: 635–642.PubMedCrossRefGoogle Scholar
  5. 5.
    Jayaraman, T., V. Berenstein, X. Li, J. Mayer, M. Silane, Y.S. Shin, et al. 2005. Tumor necrosis factor alpha is a key modulator of inflammation in cerebral aneurysms. Neurosurgery 57: 558–564.PubMedCrossRefGoogle Scholar
  6. 6.
    Ait-Oufella, H., S. Taleb, Z. Mallat, and A. Tedgui. 2011. Recent advances on the role of cytokines in atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 31: 969–979.PubMedCrossRefGoogle Scholar
  7. 7.
    Sprague, A.H., and R.A. Khalil. 2009. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochemical Pharmacology 78: 539–552.PubMedCrossRefGoogle Scholar
  8. 8.
    Tedgui, A., and Z. Mallat. 2006. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiological Reviews 86: 515–581.PubMedCrossRefGoogle Scholar
  9. 9.
    Petrasek, J., S. Bala, T. Csak, D. Lippai, K. Kodys, V. Menashy, et al. 2012. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. Journal of Clinical Investigation 122: 3476–3489.PubMedCrossRefGoogle Scholar
  10. 10.
    Oliphant, C.J., J.L. Barlow, and A.N. McKenzie. 2011. Insights into the initiation of type 2 immune responses. Immunology 134: 378–385.PubMedCrossRefGoogle Scholar
  11. 11.
    Laroux, F.S. 2004. Mechanisms of inflammation: the good, the bad and the ugly. Frontiers in Bioscience 9: 3156–3162.PubMedCrossRefGoogle Scholar
  12. 12.
    Chyatte, D., G. Bruno, S. Desai, and D.R. Todor. 1999. Inflammation and intracranial aneurysms. Neurosurgery 45: 1137–1146.PubMedCrossRefGoogle Scholar
  13. 13.
    Frosen, J., A. Piippo, A. Paetau, M. Kangasniemi, M. Niemela, J. Hernesniemi, et al. 2004. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35: 2287–2293.PubMedCrossRefGoogle Scholar
  14. 14.
    Fukuda, S., N. Hashimoto, H. Naritomi, I. Nagata, K. Nozaki, S. Kondo, et al. 2000. Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase. Circulation 101: 2532–2538.PubMedCrossRefGoogle Scholar
  15. 15.
    Moriwaki, T., Y. Takagi, N. Sadamasa, T. Aoki, K. Nozaki, and N. Hashimoto. 2006. Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice. Stroke 37: 900–905.PubMedCrossRefGoogle Scholar
  16. 16.
    Jayaraman, T., A. Paget, Y.S. Shin, X. Li, J. Mayer, H. Chaudhry, et al. 2008. TNF-alpha mediated inflammation in cerebral aneurysms: a potential link to growth and rupture. Vascular Health and Risk Management 4: 805–817.PubMedGoogle Scholar
  17. 17.
    Munoz, J., A. Albillos, M. Perez-Paramo, I. Rossi, and M. Alvarez-Mon. 1999. Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats. American Journal of Physiology 276: G687–693.PubMedGoogle Scholar
  18. 18.
    Gonzalez, C.F., Y.I. Cho, H.V. Ortega, and J. Moret. 1992. Intracranial aneurysms: flow analysis of their origin and progression. American Journal of Neuroradiology 13: 181–188.PubMedGoogle Scholar
  19. 19.
    Hoi, Y., H. Meng, S.H. Woodward, B.R. Bendok, R.A. Hanel, L.R. Guterman, et al. 2004. Effects of arterial geometry on aneurysm growth: three-dimensional computational fluid dynamics study. Journal of Neurosurgery 101: 676–681.PubMedCrossRefGoogle Scholar
  20. 20.
    Jou, L.D., G. Wong, B. Dispensa, M.T. Lawton, R.T. Higashida, W.L. Young, et al. 2005. Correlation between lumenal geometry changes and hemodynamics in fusiform intracranial aneurysms. American Journal of Neuroradiology 26: 2357–2363.PubMedGoogle Scholar
  21. 21.
    Hartel, C., N. Adam, T. Strunk, P. Temming, M. Muller-Steinhardt, and C. Schultz. 2005. Cytokine responses correlate differentially with age in infancy and early childhood. Clinical and Experimental Immunology 142: 446–453.PubMedGoogle Scholar
  22. 22.
    Ferreri, N.R. 2007. Estrogen-TNF interactions and vascular inflammation. American Journal of Physiology. Heart and Circulatory Physiology 292: H2566–2569.PubMedCrossRefGoogle Scholar
  23. 23.
    Lanzke, N., R. Kleinwachter, S. Kerschischnik, L. Sargsyan, D.A. Groneberg, T. Kamradt, et al. 2007. Differential effects of ethanol on IFN-gamma- and TNF-alpha-producing splenic T lymphocytes in a murine model of gram-negative pneumonia. Addiction Biology 12: 59–68.PubMedCrossRefGoogle Scholar
  24. 24.
    Ajuebor, M.N., R.J. Flower, R. Hannon, M. Christie, K. Bowers, A. Verity, et al. 1998. Endogenous monocyte chemoattractant protein-1 recruits monocytes in the zymosan peritonitis model. Journal of Leukocyte Biology 63: 108–116.PubMedGoogle Scholar
  25. 25.
    Kurth, I., K. Willimann, P. Schaerli, T. Hunziker, I. Clark-Lewis, and B. Moser. 2001. Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development. The Journal of Experimental Medicine 194: 855–861.PubMedCrossRefGoogle Scholar
  26. 26.
    Chensue, S.W., K.S. Warmington, N.W. Lukacs, P.M. Lincoln, M.D. Burdick, R.M. Strieter, et al. 1995. Monocyte chemotactic protein expression during schistosome egg granuloma formation. Sequence of production, localization, contribution, and regulation. American Journal of Pathology 146: 130–138.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Hai-Feng Zhang
    • 1
  • Ming-Guang Zhao
    • 1
  • Guo-Biao Liang
    • 1
  • Zhen-Quan Song
    • 1
  • Zhi-Qing Li
    • 1
  1. 1.Department of NeurosurgeryThe General Hospital of Shenyang Military RegionShenyangChina

Personalised recommendations