Interleukin -17 Serum Levels and Polymorphisms in Acute Kidney Injury Patients

Author(s): Mahsa Rahimzadeh, Hossein Montazerghaem, Sara A. Chegeni, Nadereh Naderi*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 20 , Issue 3 , 2020

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Graphical Abstract:


Background: Cardiopulmonary bypass (CPB) has been demonstrated to provoke a systemic inflammatory response believed to be responsible for some of the serious postoperative complications such as renal dysfunction. Therefore, we tested the hypothesis suggesting that the serum levels of IL- 17A (IL-17), as an inflammatory cytokine, and its gene variants are associated with acute kidney injury after CPB (AKI-CPB).

Methods: A total of 135 Iranian patients undergoing cardiopulmonary bypass were included in this study, of whom 65 (48.1%) developed AKI. Blood specimens were collected preoperatively and at 12 hours postoperatively. The IL-17 gene polymorphisms (rs2275913 and rs3819024) were determined using sequence-specific primers (PCR-SSP) technique.Pre- and postoperative IL-17 levels were measured and analyzed in relation to polymorphisms.

Results: IL-17 concentrations in CBP subjects, were increased after cardiopulmonary bypass (P<0.00001)but there were no statistically significant differences in IL-17 serum level between AKI and non-AKI groups. Different genotypes of IL-17 rs2275913 SNP (G→A) were associated with different circulating IL-17 levels before bypass and also after AKI development. There were no associations between gene polymorphisms (rs2275913and rs3819024) and incidence of AKI- CPB. There was an association between thers2275913 SNP and the severity of AKI.

Conclusion: This study clarified that the rs2275913 SNP to some extent determines plasma IL-17 concentrations in CPB patients. No significant association was found between IL-17 levels or gene polymorphisms (rs2275913and rs3819024) and incidence of AKI-CPB. Our results suggest that there is an association between rs2275913 and the severity of AKI- CPB.

Keywords: Acute kidney injury, cardiac surgery, cardiopulmonary bypass, polymorphism, IL-17, inflammation.

Yuan, S-M. Acute Kidney Injury after Cardiac Surgery: Risk Factors and Novel Biomarkers. Rev. Bras. Cir. Cardiovasc., 2019, 34(3), 352-360.
[] [PMID: 31310475]
Chew, S.T.H.; Hwang, N.C. Acute kidney injury after cardiac surgery: A narrative review of the literature. J. Cardiothorac. Vasc. Anesth., 2019, 33(4), 1122-1138.
[] [PMID: 30228051]
Vives, M.; Hernandez, A.; Parramon, F.; Estanyol, N.; Pardina, B.; Muñoz, A.; Alvarez, P.; Hernandez, C. Acute kidney injury after cardiac surgery: prevalence, impact and management challenges. Int. J. Nephrol. Renovasc. Dis., 2019, 12, 153-166.
[] [PMID: 31303781]
Singbartl, K.; Formeck, C.L.; Kellum, J.A. Kidney-immune system crosstalk in AKI.Seminars in nephrology; Elsevier, 2019.
Alexiou, C.; Tang, A.A.; Sheppard, S.V.; Smith, D.C.; Gibbs, R.; Livesey, S.A.; Monro, J.L.; Haw, M.P. The effect of leucodepletion on leucocyte activation, pulmonary inflammation and respiratory index in surgery for coronary revascularisation: a prospective randomised study. Eur. J. Cardiothorac. Surg., 2004, 26(2), 294-300.
[] [PMID: 15296886]
Wang, H.; Ma, S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am. J. Emerg. Med., 2008, 26(6), 711-715.
[] [PMID: 18606328]
Gaffen, S.L. An overview of IL-17 function and signaling. Cytokine, 2008, 43(3), 402-407.
[] [PMID: 18701318]
Kostareva, O.S.; Gabdulkhakov, A.G.; Kolyadenko, I.A.; Garber, M.B.; Tishchenko, S.V. Interleukin-17: Functional and Structural Features, Application as a Therapeutic Target. Biochemistry (Mosc.), 2019, 84(1)(Suppl. 1), S193-S205.
[] [PMID: 31213202]
Chan, A.J.; Alikhan, M.A.; Odobasic, D.; Gan, P.Y.; Khouri, M.B.; Steinmetz, O.M.; Mansell, A.S.; Kitching, A.R.; Holdsworth, S.R.; Summers, S.A. Innate IL-17A-producing leukocytes promote acute kidney injury via inflammasome and Toll-like receptor activation. Am. J. Pathol., 2014, 184(5), 1411-1418.
[] [PMID: 24631024]
Pindjakova, J.; Hanley, S.A.; Duffy, M.M.; Sutton, C.E.; Weidhofer, G.A.; Miller, M.N.; Nath, K.A.; Mills, K.H.; Ceredig, R.; Griffin, M.D. Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction. Kidney Int., 2012, 81(4), 379-390.
[] [PMID: 21975862]
Dong, X.; Bachman, L.A.; Miller, M.N.; Nath, K.A.; Griffin, M.D. Dendritic cells facilitate accumulation of IL-17 T cells in the kidney following acute renal obstruction. Kidney Int., 2008, 74(10), 1294-1309.
[] [PMID: 18974760]
Mehta, R.L.; Kellum, J.A.; Shah, S.V.; Molitoris, B.A.; Ronco, C.; Warnock, D.G.; Levin, A. Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit. Care, 2007, 11(2), R31.
[] [PMID: 17331245]
Chobanian, A.V.; Bakris, G.L.; Black, H.R.; Cushman, W.C.; Green, L.A.; Izzo, J.L., Jr; Jones, D.W.; Materson, B.J.; Oparil, S.; Wright, J.T., Jr; Roccella, E.J. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA, 2003, 289(19), 2560-2572.
[] [PMID: 12748199]
Isailovic, N.; Daigo, K.; Mantovani, A.; Selmi, C. Interleukin-17 and innate immunity in infections and chronic inflammation. J. Autoimmun., 2015, 60, 1-11.
[] [PMID: 25998834]
Hirai, S. Systemic inflammatory response syndrome after cardiac surgery under cardiopulmonary bypass. Ann. Thorac. Cardiovasc. Surg., 2003, 9(6), 365-370.
[PMID: 15003097]
Warltier, D.; Laffey, J.G.; Boylan, J.F.; Cheng, D.C. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology, 2002, 97(1), 215-252.
[] [PMID: 12131125]
Brix-Christensen, V.; Tønnesen, E.; Hjortdal, V.E.; Chew, M.; Flø, C.; Marqversen, J.; Hansen, J.F.; Andersen, N.T.; Ravn, H.B. Neutrophils and platelets accumulate in the heart, lungs, and kidneys after cardiopulmonary bypass in neonatal pigs. Crit. Care Med., 2002, 30(3), 670-676.
[] [PMID: 11990932]
Wan, S.; LeClerc, J.-L.; Vincent, J.-L. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies chest, 1997, 112(3), 676-692.
Valeri, M.; Raffatellu, M. Cytokines IL-17 and IL-22 in the host response to infection. Pathog. Dis., 2016, 74(9)ftw111
[] [PMID: 27915228]
Cooper, A.M. IL-23 and IL-17 have a multi-faceted largely negative role in fungal infection. Eur. J. Immunol., 2007, 37(10), 2680-2682.
[] [PMID: 17899544]
Lindén, A.; Adachi, M. Neutrophilic airway inflammation and IL-17. Allergy, 2002, 57(9), 769-775.
[] [PMID: 12169171]
Fossiez, F.; Djossou, O.; Chomarat, P.; Flores-Romo, L.; Ait-Yahia, S.; Maat, C.; Pin, J.J.; Garrone, P.; Garcia, E.; Saeland, S.; Blanchard, D.; Gaillard, C.; Das Mahapatra, B.; Rouvier, E.; Golstein, P.; Banchereau, J.; Lebecque, S. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J. Exp. Med., 1996, 183(6), 2593-2603.
[] [PMID: 8676080]
Royston, D.; Fleming, J.S.; Desai, J.B.; Westaby, S.; Taylor, K.M. Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation. J. Thorac. Cardiovasc. Surg., 1986, 91(5), 759-766.
[PMID: 3702483]
Miller, B.E.; Levy, J.H. The inflammatory response to cardiopulmonary bypass. J. Cardiothorac. Vasc. Anesth., 1997, 11(3), 355-366.
[] [PMID: 9161905]
Tang, A.T.; Alexiou, C.; Hsu, J.; Sheppard, S.V.; Haw, M.P.; Ohri, S.K. Leukodepletion reduces renal injury in coronary revascularization: a prospective randomized study. Ann. Thorac. Surg., 2002, 74(2), 372-377.
[] [PMID: 12173815]
Olivencia-Yurvati, A. Strategic leukocyte depletion reduces pulmonary microvascular pressure and improves pulmonary status post-cardiopulmonary bypass. Perfusion, 2003.18(1_suppl), 23-31.
Bronicki, R.A.; Hall, M. Cardiopulmonary bypass-induced inflammatory response: Pathophysiology and treatment. Pediatric Critical Care Medicine, 2016.17(8_suppl), S272-S278.
Rolandelli, A.; Hernández Del Pino, R.E.; Pellegrini, J.M.; Tateosian, N.L.; Amiano, N.O.; de la Barrera, S.; Casco, N.; Gutiérrez, M.; Palmero, D.J.; García, V.E. The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina. Sci. Rep., 2017, 7, 40666.
[] [PMID: 28098168]
Dai, Z-M.; Zhang, T.S.; Lin, S.; Zhang, W.G.; Liu, J.; Cao, X.M.; Li, H.B.; Wang, M.; Liu, X.H.; Liu, K.; Li, S.L.; Dai, Z.J. Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis. Sci. Rep., 2016, 6, 20439.
[] [PMID: 26843459]
Liu, X.K.; Lin, X.; Gaffen, S.L. Crucial role for nuclear factor of activated T cells (NFAT) in T cell receptor-mediated regulation of human interleukin-17. J. Biol. Chem., 2004.
Xue, L.; Xie, K.; Han, X.; Yang, Z.; Qiu, J.; Zhao, Z.; Bao, T. Detrimental functions of IL-17A in renal ischemia-reperfusion injury in mice. J. Surg. Res., 2011, 171(1), 266-274.
[] [PMID: 20400117]
Li, L.; Huang, L.; Vergis, A.L.; Ye, H.; Bajwa, A.; Narayan, V.; Strieter, R.M.; Rosin, D.L.; Okusa, M.D. IL-17 produced by neutrophils regulates IFN-γ-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J. Clin. Invest., 2010, 120(1), 331-342.
[] [PMID: 20038794]
Paust, H-J.; Turner, J.E.; Steinmetz, O.M.; Peters, A.; Heymann, F.; Hölscher, C.; Wolf, G.; Kurts, C.; Mittrücker, H.W.; Stahl, R.A.; Panzer, U. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. J. Am. Soc. Nephrol., 2009, 20(5), 969-979.
[] [PMID: 19339380]
Madhur, M.S.; Lob, H.E.; McCann, L.A.; Iwakura, Y.; Blinder, Y.; Guzik, T.J.; Harrison, D.G. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension, 2010, 55(2), 500-507.
[] [PMID: 20038749]
Pisitkun, P.; Ha, H.L.; Wang, H.; Claudio, E.; Tivy, C.C.; Zhou, H.; Mayadas, T.N.; Illei, G.G.; Siebenlist, U. Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis. Immunity, 2012, 37(6), 1104-1115.
[] [PMID: 23123062]
Zenobia, C.; Hajishengallis, G. Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol. 2000, 2015, 69(1), 142-159.
[] [PMID: 26252407]
Hsing, C-H.; Hsieh, M.Y.; Chen, W.Y.; Cheung So, E.; Cheng, B.C.; Chang, M.S. Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass. Ann. Thorac. Surg., 2006, 81(6), 2196-2201.
[] [PMID: 16731153]

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Year: 2020
Page: [400 - 408]
Pages: 9
DOI: 10.2174/1871530319666191009152048
Price: $65

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