Summary
Cardiopulmonary bypass (CPB) is associated with an inflammatory response, mainly caused by the trauma of surgery, contact of blood with the artificial surface of the circuit, and reperfusion injury, resulting in increased capillary permeability, respiratory distress, low cardiac output, and multiorgan failure. The inflammatory reaction includes an activation of the humoral and cellular immune system with enhanced release of cytokines. The present study focused on the effect of CPB on the time course of pro- and anti-inflammatory cytokines. In 20 patients undergoing coronary artery bypass grafting, the plasma concentration of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, and IL-10 was investigated pre-, intra-, and postoperatively by enzyme-linked immunosorbent assay technique. With the exception of IFN-γ, all the other cytokines could be detected in the patients plasma. However, neither TNF-α nor IL-1β and IL-2 revealed significant changes in concentration during the investigated time period. In contrast, IL-6 and IL-8 levels peaked early postoperatively, reaching median concentrations of 430 pg/ml (221 pg per ml/558 pg per ml; lower/upper quartiles, respectively) and approximately 12 pg/ml (0/17 pg/ml; lower/upper quartiles, respectively). IL-4 and IL-10, respectively, revealed maximal concentrations of approximately 2 pg/ml (0/39 pg/ml; lower/upper quartiles, respectively) and 208 pg/ml (76 pg per ml/380 pg per ml; lower/upper quartiles, respectively) immediately after protamine administration, preceding the maximal concentration of IL-6. The degree of the observed modulation of cytokine patterns during and after CPB seemed to be patient-dependent, since large interindividual variations in cytokine levels were observed, not only preoperatively, but especially during and following CPB. However, IL-6 and IL-10 showed the least interindividual variations, suggesting that these cytokines may give reliable information regarding modulation of the immune response following CPB and its consequences for the patient’s outcome.
Similar content being viewed by others
References
Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD (1983) Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 86:845–857
Bonser RS, Dave J, Gademsetty M, Carter P, Davies E, Taylor P, Gaya H, Lennox SC, Vergani D (1990) Complement activation before, during and after cardiopulmonary bypass. Eur J Cardiothorac Surg 4:291–296
Babin-Ebell J, Neukam K, Steinbrückner BE, Steigerwald U, Keller F, Elert O (1995) Aktivierung von Gerinnung und Fibrinolyse während der extrakorporalen Zirkulation — Einfluß von Rollerpumpe, Zentrifugalpumpe und heparinbeschichteten Oberflächen. Z Herz-, Thorax-, Gefäßchir 9:196–204
Steinbrückner BE, Steigerwald U, Keller F, Neukam K, Elert O, Babin-Ebell J (1995) Centrifugal and roller pumps — are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass? Heart Vessels 10:46–53
Grossmann R, Babin-Ebell J, Misoph M, Schwender S, Neukam K, Hickethier Th, Elert O, Keller F (1996) Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation. Heart Vessels 11:310–317
Tanaka K, Morimoto T, Yada I, Kusagawa M, Deguchi K (1987) Physiologic role of enhanced fibrinolytic activity during cardiopulmonary bypass in open heart surgery. Trans Am Soc Artif Intern Organs 33:505–509
Schmid FX, Zhou X, Hake U, Mayer E, Habermehl P, Zepp F, Eberle B, Oelert H (1996) Zell-vermittelter Immunstatus während und nach Operationen mit und ohne extrakorporaler Zirkulation. Z Herz-, Thorax-, Gefäßchir 10:153–161
Steinberg JB, Kapelanski DP, Olson JD, Weiler JM (1993) Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 106:1008–1016
Hashimoto K, Miyamoto H, Suzuki K, Horikoshi S, Matsui M, Arai T, Kurosawa H (1992) Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators. J Thorac Cardiovasc Surg 104(3):666–673
Shenkin A, Fraser WD, Series J, Winstanley FP, McCartney AC, Burns HJ, Van-Damme J (1989) The serum interleukin 6 response to elective surgery. Lymphokine Res 8:123–127
Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H (1987) Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci 84:7251–7255
Kawamura T, Wakusawa R, Kazutoshi O, Inada S (1993) Elevation of cytokines during open heart surgery with cardiopulmonary bypass: Participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth 40:1016–1021
Casey LC (1993) Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. Ann Thorac Surg 56:92–96
Frering B, Philip I, Dehoux M, Rolland C, Langlois JM, Desmonts JM (1994) Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg 108:636–641
Kawahito K, Kawakami M, Fujiwara T, Murata S, Yamaguchi A, Mizuhara A, Adachi H, Ino T (1995) Proinflammatory cytokine levels in patients undergoing cardiopulmonary bypass. Does lung reperfusion influence the release of cytokines? ASAIO J 41:M775–778
Steinberg BM, Grossi EA, Schwartz DS, McLoughlin DE, Aguinaga M, Bizekis C, Greenwald J, Flisser A, Spencer FC, Galloway AC, Colvin SB (1995) Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. Ann Thorac Surg 60:525–529
Misoph M, Babin-Ebell J, Schwender S, Grossmann R, Keller F, Elert O (1997) Response of the cellular immune system to cardiopulmonary bypass in vivo. Thorac Cardiovasc Surg 45
Nijsten MW, de Groot ER, ten Duis HJ, Klasen HJ, Hack CE, Aarden LA (1987) Serum levels of interleukin 6 and acute phase responses. Lancet II (8564):921
Stouthard JM, Levi M, Hack CE, Veenhof CHN, Romijn HA, Sauerwein HP, van der Poll T (1996) Interleukin-6 stimulates coagulation, not fibrindysis, in humans. Thromb Haemost 76:738–742
Borowiec JW, Hagman L, Tötterman TH, Pekna M, Venge P, Thelin S (1995) Circulating cytokines and granulocyte-derived enzymes during complex heart surgery. Scand J Thor Cardiovasc Surg 29:167–174
Cruickshank AM, Fraser WD, Burns HJ, Van-Damme J, Shenkin A (1990) Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci Cokh 79:161–165
Butler 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 53:833–838
Wan S, DeSmet JM, Barvais L, Goldstein M, Vincent JL, LeClerk JL (1996) Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 112:806–811
Kukielka GL, Smith CW, Manning AM, Youker KA, Michael LH, Entman ML (1995) Induction of interleukin-6 synthesis in the myocardium. Circulation 92:1866–1875
Dauber IM, Parsons PE, Welsh CH, Giclas PC, Whitman GJR, Wheeler GS, Horwitz LD, Weil JV (1993) Peripheral bypass-induced pulmonary and coronary vascular injury. Circulation 88:726–735
Hattler BG, Zeevi A, Oddis CV, Finkel MS (1995) Cytokine induction during cardiac surgery: Analysis of TNF-alpha expression pre- and postcardiopulmonary bypass. J Card Surg 10 [4 Suppl]:418–422
Haeffner-Cavaillon N, Roussellier N, Ponzio O, Carreno MP, Laude M, Carpentier A, Kazatchkine MD (1989) Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 98:1100–1106
Deng MC, Wiedner M, Erren M, Möllhoff T, Assmann G, Scheld HH (1995) Arterial and venous cytokine response to cardiopulmonary bypass for low risk CABG and relation to hemodynamics. Eur J Cardiothorac Surg 9:22–29
Markewitz A, Faist E, Lang S, Endres S, Hültner L, Reichart B (1993) Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. Ann Thorac Surg 55:389–394
Markewitz A, Faist E, Lang S, Endres S, Fuchs D, Reichart B (1993) Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation. J Thorac Cardiovasc Surg 105:15–24
Finn A, Naik S, Klein N, Levinsky R, Strobel S, Elliott M (1993) Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 105:234–241
Kunkel SL, Standiford T, Kasahara K, Strieter RM (1991) Interleukin-8 (IL-8): The major neutrophil chemotactic factor in the lung. Exp Lung Res 17:17–23
Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, Leung JM, Mangano DT, Greenfield LJ, Rankin JS (1994) Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg 108:626–635
Burns SA, Newburger JW, Xiao M, Mayer JE, Walsh AZ, Neufeld EJ (1995) Induction of interleukin-8 messenger RNA in heart and skeletal muscle during pediatric cardiopulmonary bypass. Circulation 92 [Suppl II]:315–321
Lee JD, Rhoades K, Economou JS (1995) Interleukin-4 inhibits the expression of tumor necrosis factors alpha and beta, interleukin-1 beta and -6 and interferon-gamma. Immunol Cell Biol 73:57–61
Standiford TJ, Strieter RM, Chensue SW, Westwick J, Kasahara K, Kunkel SL (1990) IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol 145:1435–1439
Daftarian PM, Kumar A, Kryworuchko M, Diaz-Mitoma F (1996) IL-10 production is enhanced in human T cells by IL-12 and IL-6 and in monocytes by tumor necrosis factor-alpha. J Immunol 157:12–20
Tabardel Y, Duchateau J, Schmartz D, Marecaux G, Shahla M, Barvais L, Leclerc JL, Vincent JL (1996) Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery 119:76–80
Seghaye M, Duchateau J, Bruniaux J, Demontoux S, Bosson C, Serraf A, Lecronier G, Mokhfi E, Planche C (1996) Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg 111:545–553
McBride WT, Armstrong MA, Crockard AD, McMurray TJ, Rea JM (1995) Cytokine balance and immunosuppressive changes at cardiac surgery: Contrasting response between patients and isolated CPB circuits. Br J Anaesth 75:724–733
Berger S, Ballo H, Stutte HJ (1996) Immune complex-induced interleukin-6, interleukin-10 and prostaglandin secretion by human monocytes: A network of pro- and anti-inflammatory cytokines dependent on the antigen: antibody ratio. Eur J Immunol 26:1297–1301
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Misoph, M., Babin-Ebell, J. Interindividual variations in cytokine levels following cardiopulmonary bypass. Heart Vessels 12, 119–127 (1997). https://doi.org/10.1007/BF02767129
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02767129