The Impact of Serum Interleukin-4, Interleukin-10, Interleukin-17a, and Interleukin-22 Levels on the Development of Sporadic Ascending Aortic Aneurysms

Yıl 2023, Cilt: 26 Sayı: 3, 99 - 106, 21.11.2023

Ulaankhuu Batgerel Ayça Özgen Gaye Erten

Öz

Introduction: Aortic aneurysms are chronic diseases associated with inflammatory/immunological mechanisms. Interleukins (ILs) with pro-inflammatory and anti-inflammatory activities are shown to be related to the development of aortic damage. In this context, this study aims to evaluate the serum IL-4, IL-10, IL-17A, and IL-22 in patients with sporadic thoracic ascending aortic aneurysms.

Patients and Methods: The population of this prospective study consisted of all consecutive patients with sporadic ascending aortic aneurysms who underwent thoracic aortic aneurysm repair between November 2019 and September 2022. In the end, 29 patients (the patient group) and 19 healthy voluntary participants without aortic pathology (the control group) were included in the study. The study’s primary outcome was the differences in serum IL levels between the groups.

Results: The patient group was significantly older than the control group (p= 0.042). Significantly higher neutrophil-to-lymphocyte ratio (NLR) values were detected in the patient group (p= 0.031). The median IL10 (p= 0.001), IL-17A (p< 0.001), and IL-4 (p< 0.001) levels were significantly lower in the patient group than in the control group. There were no significant correlations between serum IL levels and the aneurysm diameter (p> 0.05). On the other hand, there were moderate correlations between IL-10 and IL-17A (r= 0.409, p= 0.038), IL-10 and IL-22 (r= 0.464, p= 0.017), and IL-17A and IL-4 (r= 0.496, p= 0.006). NLR ≥1.95 was found to be an independent risk factor for sporadic ascending aortic aneurysms [Odds Ratio (OR)= 4.53, 95% confidence interval (CI)= 1.12-21.17, p= 0.040].

Conclusion: IL-10, IL-17A, and IL-4 were significantly lower in patients with sporadic ascending aortic aneurysms larger than 55 mm. NLR was an independent risk factor for sporadic ascending aortic aneurysms. The diameter of the aneurysm was not correlated with ILs. There were positive correlations between IL-10, IL-17A, and IL-4 levels.

Anahtar Kelimeler

Ascending aorta, inflammation, interleukins

Kaynakça

• 1. Jud P, Verheyen N, Stradner MH, Dejaco C, Szolar D, Thonhofer R, et al. Association of immunological parameters with aortic dilatation in giant cell arteritis: A cross-sectional study. Rheumatol Int 2023;43(3):477-85. https://doi.org/10.1007/s00296-022-05186-1
• 2. Scola L, Di Maggio FM, Vaccarino L, Bova M, Forte GI, Pisano C, et al. Role of TGF-β pathway polymorphisms in sporadic thoracic aortic aneurysm: rs900 TGF-β2 is a marker of differential gender susceptibility. Mediators Inflamm 2014;2014:165758. https://doi.org/10.1155/2014/165758
• 3. Lim WW, Dong J, Ng B, Widjaja AA, Xie C, Su L, et al. Inhibition of IL11 signaling reduces aortic pathology in murine marfan syndrome. Circ Res 2022;130(5):728-40. https://doi.org/10.1161/CIRCRESAHA.121.320381
• 4. Fujita D, Preiss L, Aizawa K, Asch F, Eagle K, Suzuki T; GenTAC registry investigators. Circulating interleukin-6 (IL-6) levels are associated with aortic dimensions in genetic aortic conditions. PLoS One 2019;14(3):e0214084. https://doi.org/10.1371/journal.pone.0214084
• 5. Kasashima S, Kawashima A, Zen Y, Ozaki S, Kasashima F, Endo M, et al. Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4-related aortic aneurysm patients. J Vasc Surg 2018;67(4):1248-62. https://doi.org/10.1016/j.jvs.2016.12.140
• 6. Salmon M, Hawkins RB, Dahl J, Scott E, Johnston WF, Ailawadi G. Genetic and pharmacological disruption of interleukin-1α leads to augmented murine aortic aneurysm. Ann Vasc Surg 2022;85:358-70. https://doi.org/10.1016/j.avsg.2022.05.024
• 7. Wortmann M, Peters AS, Erhart P, Körfer D, Böckler D, Dihlmann S. Inflammasomes in the pathophysiology of aortic disease. Cells 2021;15:10(9):2433. https://doi.org/10.3390/cells10092433
• 8. Adam M, Kooreman NG, Jagger A, Wagenhäuser MU, Mehrkens D, Wang Y, et al. Systemic upregulation of IL-10 (Interleukin-10) using a nonimmunogenic vector reduces growth and rate of dissecting abdominal aortica aneurysm. Arterioscler Thromb Vasc Biol 2018;38(8):1796-805. https://doi.org/10.1161/ATVBAHA.117.310672
• 9. Ahmad M, Kuravi S, Hodson J, Rainger GE, Nash GB, Vohra RK, et al. The relationship between serum interleukin-1α and asymptomatic infrarenal abdominal aortic aneurysm size, morphology, and growth rates. Eur J Vasc Endovasc Surg 2018;56(1):130-5. https://doi.org/10.1016/j.ejvs.2018.01.015
• 10. Batra R, Suh MK, Carson JS, Dale MA, Meisinger TM, Fitzgerald M, et al. IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) impact abdominal aortic aneurysm formation by differential effects on macrophage polarization. Arterioscler Thromb Vasc Biol 2018;38(2):457-63. https://doi.org/10.1161/ATVBAHA.117.310333
• 11. Akerman AW, Stroud RE, Barrs RW, Grespin RT, McDonald LT, LaRue RAC, et al. Elevated wall tension initiates interleukin-6 expression and abdominal aortic dilation. Ann Vasc Surg 2018;46:193-204. https://doi.org/10.1016/j.avsg.2017.10.001
• 12. Wang Y, Li J, Xu Y, Liao S, Song J, Xu Z, et al. Interleukin-22 deficiency reduces angiotensin II-induced aortic dissection and abdominal aortic aneurysm in ApoE-/- Mice. Oxid Med Cell Longev 2022;2022:7555492. https://doi.org/10.1155/2022/7555492
• 13. Tanaka H, Xu B, Xuan H, Ge Y, Wang Y, Li Y, et al. Recombinant interleukin-19 suppresses the formation and progression of experimental abdominal aortic aneurysms. J Am Heart Assoc 2021;10(17):e022207. https://doi.org/10.1161/JAHA.121.022207
• 14. Bengts S, Shamoun L, Kunath A, Appelgren D, Welander M, Björck M, et al. Altered IL-32 signaling in abdominal aortic aneurysm. J Vasc Res 2020;57(4):236-44. https://doi.org/10.1159/000507667
• 15. Kurose S, Matsubara Y, Yoshino S, Yoshiya K, Morisaki K, Furuyama T, et al. Interleukin-38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2-p38 pathway-dependent manner. Physiol Rep 2023;11(2):e15581. https://doi.org/10.14814/phy2.15581
• 16. Zhang L, Liao MF, Tian L, Zou SL, Lu QS, Bao JM, et al. Overexpression of interleukin-1β and interferon-γ in type I thoracic aortic dissections and ascending thoracic aortic aneurysms: Possible correlation with matrix metalloproteinase-9 expression and apoptosis of aortic media cells. Eur J Cardiothorac Surg 2011;40(1):17-22. https://doi.org/10.1016/j.ejcts.2010.09.019
• 17. Scola L, Giarratana RM, Marinello V, Cancila V, Pisano C, Ruvolo G, et al. Polymorphisms of pro-inflammatory IL-6 and IL-1β cytokines in ascending aortic aneurysms as genetic modifiers and predictive and prognostic biomarkers. Biomolecules 2021;11(7):943. https://doi.org/10.3390/biom11070943
• 18. Wortmann M, Klotz R, Kalkum E, Dihlmann S, Böckler D, Peters AS. Inflammasome targeted therapy as novel treatment option for aortic aneurysms and dissections: A systematic review of the preclinical evidence. Front Cardiovasc Med 2022;20;8:805150. https://doi.org/10.3389/fcvm.2021.805150
• 19. Åström Malm I, De Basso R, Blomstrand P, Wågsäter D. Association of IL-10 and CRP with pulse wave velocity in patients with abdominal aortic aneurysm. J Clin Med 2022;11(5):1182. https://doi.org/10.3390/jcm11051182
• 20. Saura D, Dulgheru R, Caballero L, Bernard A, Kou S, Gonjilashvili N, et al. Two-dimensional transthoracic echocardiographic normal reference ranges for proximal aorta dimensions: Results from the EACVI NORRE study. Eur Heart J Cardiovasc Imaging 2017;18(2):167-79. https://doi.org/10.1093/ehjci/jew053
• 21. Balistreri CR. Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants. Vascul Pharmacol 2015;74:1-10. https://doi.org/10.1016/j.vph.2015.09.006
• 22. Stather PW, Sidloff DA, Dattani N, Gokani VJ, Choke E, Sayers RD, et al. Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm. Br J Surg 2014;101(11):1358-72. https://doi.org/10.1002/bjs.9593
• 23. Zeng T, Shi L, Ji Q, Shi Y, Huang Y, Liu Y, et al. Cytokines in aortic dissection. Clin Chim Acta 2018;486:177-82. https://doi.org/10.1016/j.cca.2018.08.005
• 24. Puchenkova OA, Soldatov VO, Belykh AE, Bushueva O, Piavchenko GA, Venediktov AA, et al. Cytokines in abdominal aortic aneurysm: Master regulators with clinical application. Biomark Insights 2022;17:11772719221095676. https://doi.org/10.1177/11772719221095676
• 25. Parry DJ, Al-Barjas HS, Chappell L, Rashid ST, Ariëns RA, Scott DJ. Markers of inflammation in men with small abdominal aortic aneurysm. J Vasc Surg 2010;52(1):145-51. https://doi.org/10.1016/j.jvs.2010.02.279
• 26. Wallinder J, Skagius E, Bergqvist D, Henriksson AE. Early inflammatory response in patients with ruptured abdominal aortic aneurysm. Vasc Endovascular Surg 2010;44(1):32-5. https://doi.org/10.1177/1538574409339358
• 27. Cheuk BL, Cheng SW. 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):391-5. https://doi.org/10.3892/ijmm.20.3.391
• 28. Liao M, Liu CL, Lv BJ, Zhang JY, Cheng L, Cheng X, et al. Plasma cytokine levels and risks of abdominal aortic aneurysms: A population-based prospective cohort study. Ann Med 2015;47(3):245-52. https://doi.org/10.3109/07853890.2015.1019916
• 29. Dawson J, Cockerill GW, Choke E, Belli AM, Loftus I, Thompson MM. Aortic aneurysms secrete interleukin-6 into the circulation. J Vasc Surg 2007;45(2):350-6. https://doi.org/10.1016/j.jvs.2006.09.049
• 30. Sharma AK, Lu G, Jester A, Johnston WF, Zhao Y, Hajzus VA, et al. Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. Circulation 2012;126:S38-45. https://doi.org/10.1161/CIRCULATIONAHA.111.083451
• 31. Ye J, Wang M, Jiang H, Ji Q, Huang Y, Liu J, et al. Increased levels of interleukin-22 in thoracic aorta and plasma from patients with acute thoracic aortic dissection. Clin Chim Acta 2018;486:395-401. https://doi.org/10.1016/j.cca.2017.10.033