Evaluation of Systemic Inflammatory Response in Cardiovascular Surgery via Interleukin-6, Interleukin-8, and Neopterin


  • Ihsan Sami Uyar
  • Suleyman Onal
  • Ayhan Uysal
  • Ugur Ozdemir
  • Oktay Burma
  • Vedat Bulut




Aim: The aim of this study was to evaluate the serum levels of interleukin-6 (IL-6), IL-8, and neopterin as a sign of systemic inflammatory response syndrome after open-heart surgery. In this study, we evaluated the influences on the levels of IL-6, IL-8, and neopterin of coronary artery bypass grafting (CABG) and valve replacement surgeries with and without the use of extracorporeal circulation (ECC).

Materials and Methods: This prospective study was performed in 30 patients. In this study, we evaluated patients who underwent valve replacement surgery (group 1, n = 10), CABG with ECC (group 2, n = 10), or CABG using the beating-heart technique (group 3, n = 10). With the Human Investigation Ethics Committee consent, blood samples were obtained from the patients before the surgery (T0) and after 1 hour (T1), 4 hours (T2), 24 hours (T3), and 48 hours (T4) of protamine injection. IL-6, IL-8, and neopterin levels were measured using commercial enzyme-linked immunosorbent assay kits.

Results: The demographic data and preoperative and operative characteristics of the patients were similar. Neopterin IL-6 and IL-8 levels significantly increased first at the fourth hour after the surgery. When compared to the levels before the surgery, this increase was statistically significant. Unlike the other 2 groups of patients, those who experienced CABG with the beating-heart technique (group 3) had decreased neopterin levels at the first hour after the surgery, but this decrease was not statistically significant. Neopterin levels increased later in the OPCAB group, but these increased levels were not as high as the neopterin levels of groups 1 and 2. Neopterin reached maximum levels at the 24th hour and, unlike groups 1 and 2, in group started to decrease at the 48th.

Conclusions: Complement activation, cytokine production, and related cellular responses are important factors during open-heart surgery. It is certain that ECC activates the complement systems, and activated complement proteins cause the production of several cytokines. In our study, neopterin levels in patients who underwent beating-heart method surgery were lower than those in the other groups, and these levels started to decrease at the 48th hour. These data suggest that the systemic inflammatory response was less activated in that patient group. The beating-heart method might be an important alternative in CABG surgery to minimize the complications and mortality related to surgery.


Brki? K, Uni? D, Sutli? Z, et al. 2006. Neopterin kinetics after cardiac surgery with or without cardiopulmonary bypass. Coll Antropol 30:395-400.nButler J, Chong GL, Baigrie RJ, Pillai R, Westaby S, Rocker GM. 1992. Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 53:833-8.nButler J, Rocker GM, Westaby S. 1993. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 55:552-9.nCasey LC. 1993. Role of cytokines in the pathogenesis of cardiopulmonary induced multisystem organ failure. Ann Thorac Surg 56(5 Suppl):S92-6.nCremer J, Martin M, Redl H, et al. 1996. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 61:1714-20.nDecker D, Lindemann C, Low A, Bidlinghaier F, Hirner A, von Ruecker A. 1997. Changes in the cytokine concentration (Il-6, Il-8, Il-1ra) and their cellular expression of membrane molecules (CD25, CD30, HLA-DR) after surgical trauma [Article in German]. Zentralbl Chir 122:157-63.nDonati A, Batiste D, Recchioni A, et al. 1998. Predictive value of interleukin 6 (IL-6), interleukin 8 (IL-8) and gastric intramucosal pH (pH-i) in major abdominal surgery. Inten C Med 24:329-35.nHayashida N, Tomoeda H, Oda T, et al. 1999. Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass. Ann Thorac Surg 68:1661-7.nHennein HA, Ebba H, Rodriguez JL, et al. 1994. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg 108:626-35.nIvey CL, Williams FM, Collins PD, Jose PJ, Williams TJ. 1995. Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit: evidence for a role for C5a and interleukin-8. J Clin Invest 95:2720-8.nKirklin JK. The postperfusion syndrome: inflammation and the damaging effects of cardiopulmonary bypass. In: Tinker JH, ed. Cardiopulmonary bypass: current concepts and controversies, Philadelphia: WB Saunders; 1989. p:131-46.nKutay V, Noyan T, Ozcan S, Melek Y, Ekim H, Yakut C. 2006. Biocompatibility of heparin-coated cardiopulmonary bypass circuits in coronary patients with left ventricular dysfunction is superior to PMEA-coated circuits. J Card Surg 21:572-7.nPatrick DA, Moore FA, Moore EE, et al. 1996. Jack A. Barney Resident Research Award winner. The inflammatory profile of IL 6, IL 8 and soluble intercelluler adhesion molecule-1 in postinjury multiple organ failure. Am J Surg 172:425-31.nRaja SG, Berg GA. 2007. Impact of off-pump coronary artery bypass surgery on systemic inflammation: current best available evidence. J Card Surg 22:445-55.nRamlawi B, Otu H, Russo MJ, Novick RJ, Bianchi C, Sellke FW. 2009. Aprotinin attenuates genomic expression variability following cardiac surgery. J Card Surg 24:772-80.nSchulze CJ, Han L, Ghorpade N, et al. 2009. Phosphorylcholine-coated circuits improve preservation of platelet count and reduce expression of proinflammatory cytokines in CABG: a prospective randomized trial. J Card Surg 24:363-8.nTakayama H, Soltow LO, Chandler WL, Vocelka CR, Aldea GS. 2007. Does the type of surgery effect systemic response following cardiopulmonary bypass? J Card Surg 22:307-13.nUyar IS, Onal S, Akp?nar MB, et al. 2013. Alpha lipoic acid attenuates inflammatory response during extracorporeal circulation. Cardiovasc J Afr 24:343-348.nViaro F, Baldo CF, Capellini VK, et al. 2008. Plasma nitrate/nitrite (NOx) is not a useful biomarker to predict inherent cardiopulmonary bypass inflammatory response. J Card Surg 23:336-8.nWan S, DeSmet JM, Barvais L, Goldstein M, Vincent JL, LeClere JL. 1996. Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 112:806-11.nWan S, Izzat MB, Lee TW, Wan IY, Tang NL, Yim AP. 1999. Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury. Ann Thorac Surg 68:52-7.nWan S, LeClerc JL, Vincent JL. 1997. Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac transplantation. Ann Thorac Surg 63:269-76.nWan S, LeClerc JL, Vincent JL. 1997. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 112:676-92.n



How to Cite

Uyar, I. S., Onal, S., Uysal, A., Ozdemir, U., Burma, O., & Bulut, V. (2014). Evaluation of Systemic Inflammatory Response in Cardiovascular Surgery via Interleukin-6, Interleukin-8, and Neopterin. The Heart Surgery Forum, 17(1), E13-E17. https://doi.org/10.1532/HSF98.2013267




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