Plasmatic Levels of Proinflammatory Cytokines in Abdominal Aortic Aneurysms

Czech version

Authors: V. Třeška ¹; O. Topolčan ²; J. Kočová ³; J. Moláček ¹; K. Houdek ¹; Z. Tonar ³; J. Vrzalová ²; Inka Třešková ¹; V. Křížková ³; L. Boudová ³
Authors‘ workplace: Chirurgická klinika Lékařské fakulty a Fakultní nemocnice v Plzni, přednosta: prof. MUDr. Vladislav Třeška, DrSc. ¹; Oddělení imunochemické diagnostiky Lékařské fakulty a Fakultní nemocnice v Plzni, přednosta: prof. MUDr. Ondřej Topolčan, CSc. ²; Ústav histologie a embryologie Lékařské fakulty UK v Plzni, přednostka: doc. MUDr. Jitka Kočová, CSc. ³
Published in: Rozhl. Chir., 2011, roč. 90, č. 1, s. 37-41.
Category: Monothematic special - Original

Overview

Introduction:
Inflammation within the abdominal aortic wall is generally considered a very significant ethiopathogenic factor in the development of abdominal aortic aneurysms. Proinflammatory cytokines are important mediators of inflammation within the abdominal aortic wall.

Aim:
The aim of the study was to research, whether plasmatic levels of certain proinflammatory cytikens, which can commonly be evaluated (TNFα, IL-1, -2, -6 a -8), play a significant role in the development of AAA.

Method:
The prospective non- randomized study included 345 patients with AAAs. The patients were assigned to 5 subgroups based on their symptoms and AAA diameters. The first subgroup included patients with symptomatic AAAs, including AAA ruptures (N = 69), the second subgroup included subjects with asymptomatic AAAs (N = 276) with AAA diameters up to 5 cm (N = 72), the third subgroup included 5 cm (N = 72), the fourth included 5–8 cm (N = 192) and the fifth subgroup included subjects with AAA diameters of more than 8 cm (N = 81). The mean age of patients was 74.1 ± 7.8 years (56–84 y.o.a.). The male to female ratio was 5:1. The control group included 30 healthy volunteer subjects of similar age and male to female rates, who had no clinical signs of arterial disorders. Plasmatic levels of cytokines were evaluated from venous blood samples using ELISA (Bender, Austria) testing. Statistical assessment of the results was performed using ANOVA and Wilcoxon tests with Spearman’s correlation. P values< 0.05 were considered significant.

Results:
Plasmatic concentrations of proinflammatory cytokines were found to be statistically significantly higher in patients with AAAs compared to those in healthy volunteers. Plasmatic IL8 levels were significantly decreasing proportionally to decreasing AAA diameters (p < 0.05). TNFα levels were found to be significantly low in symptomatic patients with AAA ruptures (p < 0.05).

Conclusion:
The study confirmed the significance of proinflammatory cytokines levels monitoring in AAA patients. The authors showed that, for instance IL8 activity and to a certain extent TNFα activity, is the highest in small and developing AAAs. These findings would be significant for customized medication therapy aimed at blocking the effects of these factors on the inflammatory process within the AAA wall.

Key words:
abdominal aortic aneurysm– proinflammatory cytokines

Sources

1. Chaikof, E. L., Brewster, D. C, Dalman, R. L., Makaroun, M. S., Illig, K. A., Sicard, G. A., Timaran, C. H., Upchurch, G. R., Veith, F. J. The care of patiens with abdominal aortic aneurysma: the Society for Vascular Surgery practice guidelines. J. Vasc. Surg., 2009; 50 (4Suppl): S2–49.

2. Nordon, I. M., Hinchliffe, R. J., Holt, P. J., Loftus, I. M., Thompson, M. M. Review of current theories for abdominal aortic aneurysma pathogenesis. Vascular, 2009; 17(5): 253–263.

3. Reeps, C., Pelisek, J., Seidl, S., Schuster, T., Zimmermann, A., Kuehnl, A., Eckstein, H. H. Inflammatory infiltrates and neovessels are relevant sources of MMPs in abdominal aortic aneurysm wall. Pathobiology, 2009; 76(5): 243–252.

4. Treska,V., Kocova, J., Topolcan, O., Boudova, L. Inflammation in the wall of abdominal aneurysm and its role for symptomatology of aneurysm. Cytokines, Cellular and Molecular Therapy Journal, 2002; 7(3): 91–97.

5. Tonar, Z., Nemecek, S., Holota, R., Kocova, J., Treska, V., Molacek, J., Kohoutek, T., Hadravska, S. Microscopic image analysis of elastin network in samples of normal, atherosclerotic and aneurysmatic abdominal aorta and its biomechanical implications. J. Appl. Biomed., 2003; 1 (3): 149–160.

6. Golledge, J., Tsao, P. S., Dalman, R. L., Norman, P. E. Circulating markers of abdominal aortic aneurysm presence and progression. Circulation, 2008; 118(23): 2382–2392.

7. Ailawadi, G, Eliason, J. L., Upchurch, G. R. Jr. Current concepts in the pathogenesis of abdominal aortic aneurysm. J. Vasc. Surg., 2003; 38(3): 584–588.

8. Annambhotla, S., Bourgeois, S., Wang, X., Lin, P. H., Yao, Q., Chen, C. Recent advances in molecular mechanisms of abdominal aortic aneurysm formation. World J. Surg., 2008; 32(6): 976–986.

9. Gottsäter, A., Flondell-Site, D., Kölbel, T., Lindblad, B. Associations betweenstatin treatment and markers of inflammation, vasoconstriction, and coagulation in patients with abdominal aortic aneurysm. Vasc. Endovascular Surg., 2009; 42(6): 567–573.

10. Golledge, A. L., Walker, P., Norman, P. E., Golledge, J. A systematic review of studies examining inflammation associated cytokines in human abdominal aortic aneurysm samples. Dis. Markers, 2009; 26(4): 181–188.

11. Golledge, J., Clancy, P., Jones, G. T., Cooper, M., Palmer, L. J., van Rij, A. M., Norman, P. E. Possible association between genetic polymorphisms in transforming growth factor beta receptors, serum transforming growth factor beta1 concentration and abdominal aortic aneurysm. Br. J. Surg., 2009; 96(6): 628–632.

12. Treska, V., Topolcan, O., Wenham, P. W., Pecenm, L., Kocova, J. Cytokine metabolism in aneurysms of the abdominal aorta. Rozhl. Chir., 1998; 77(5): 225–229.

13. Borges, L. F., Touat, Z., Leclercq, A., Zen, A. A., Jondeau, G., Franc, B., Philippe, M., Meilhac, O., Gutierrez, P. S., Michel, J. B. Tissue diffusion and retention of metalloproteinases in ascending aortic aneurysma and dissections. Hum. Pathol., 2009; 40(3): 306–313.

14. Hamano, K., Li, T. S., Takahashi, M., Kobayashi, T., Shirasawa, B., Ito, H., Zempo, N. Enhanced tumor necrosis factor- alpha expression in small sized abdominal aortic aneurysms. World J. Surg., 2003; 27(4): 476–480.

15. Dawson, J., Cockerill, G., Choke, E., Loftus, I., Thompson, M. M. Circulating cytokines in patients with abdominal aortic aneurysms. Ann. N Y Acad. Sci., 2006; 1085: 324–326.

16. Guo, D. C., Papke, C. L., He, R., Milewicz, D. M. Pathogenesis of thoracic and abdominal aortic aneurysms. Ann. N Y Acad. Sci., 2006; 1085: 339–352.

17. Rizas, K. D., Ippagunta, N., Tilsom, M. D. Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. Cardiol. Rev., 2009; 17(5): 201–210.

18. Houard, X., Touat, Z., Ollivier, V., Louedec, L., Philippe, M., Sebbag, U., Meilhac, O., Rossignol, P., Michel, J. B. Mediators of neutrophil recruitment in human abdominal aortic aneurysms. Cardiovasc. Res., 2009; 82(3): 532–541.

19. Wallinder, J., Bergqvist, D,. Henriksson, A. E. Proinflammatory and anti-inflammatory cytokine balance in patients with abdominal aortic aneurysm and the impact of aneurysm size. Vasc. Endovascular Surg., 2009; 43(3): 258–261.

20. Middleton, R. K., Lloyd, G. M., Bown, M. J., Cooper, N. J., London, N. J., Sayers, R. D. The pro-inflammatory and chemotactic cytokine microenvironment of the abdominal aortic aneurysm wall: a protein array study. Eur. J. Vasc. Endovasc. Surg., 2009; 37(1): 46–55.

21. Dawson, J., Cockerill, G., Choke, E., Loftus, I., Thompson, M. M. Aortic aneurysms as a source of circulating interleukin-6. Ann. N Y Acad. Sci., 2006; 1085: 320–323.

22. Karlsson, L., Bergqvist, D., Lindback, J., Parsson, H. Expansion of small-diameter abdominal aortic aneurysms is not reflected by the release of inflammatory mediators IL-6, MMP-9 and CRP in plasma. Eur. J. Vasc. Endovasc. Surg., 2009; 37(4): 420–424.

23. Lindeman, J. H., Abdul-Hussien, H., Schaapherder, A. F., Van Bockel, J. H., von der Thüsen, J. H., Roelen, D. L., Kleemann, R. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm. Clin Sci (Lond). 2008; 114(11): 687–697.

24. Dawson, J. A., Choke, E., Cockerill, G. W., Loftus, I. M., Thompson, M. M. The long-term effects of open and endovascular aneurysm repair on circulating interleukin-6. Eur. J. Vasc. Endovasc. Surg., 2009; 37(1): 43–45.

25. Cheuk, B. L., Cheng, S. W. Differential secretion of prostaglandin E(2), thromboxane A(2) and interleukin-6 in intact and ruptured abdominal aortic aneurysms. Int. J. Mol. Med., 2007; 20(3): 391–395.

26. Xiong, W., MacTaggart, J., Knispel, R., Worth, J., Persidsky, Y., Baxter, B. T. Blocking TNF-alpha attenuates aneurysm formation in a murine model. J. Immunol., 2009; 183(4): 2741–2746.

27. Flondell-Sité, D., Lindblad, B., Kolbel, T., Gottsater, A. Cytokines and systemic biomarkers are related to the size of abdominal aortic aneurysms. Cytokine, 2009; 46(2): 211–215.

28. Zhang, L. N., Vincelette, J., Cheng, Y., Mehra, U., Chen, D., Anandan, S. K., Gless, R, Webb, H. K., Wang, Y. X. Inhibition of soluble epoxide hydrolase atenuated atherosclerosis, abdominal aortic aneurysm formativ, and dyslipidemia. Arterioscler. Thromb. Vasc. Biol., 2009; 29(9): 1265–1270.