Interindividual variations in cytokine levels following cardiopulmonary bypass

Abstract

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)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, 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-gamma, all the other cytokines could be detected in the patients plasma. However, neither TNF-alpha nor IL-1 beta 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.

Tumor necrosis factor-α –863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery

“…Tumor necrosis factor alpha (TNF-a), a pro-inflammatory cytokine, plays a key role in the post-CABG inflammatory response [7][8][9]. TNF-a level increases in response to CPB with a peak shortly after surgery and faces rapid degradation afterwards.…”

The eNOS 786C/T polymorphism in cardiac surgical patients with cardiopulmonary bypass is associated with renal dysfunction

“…Therefore, during cardiopulmonary bypass, there are substantial decreases (25-75%) in the renal blood flow and the glomerular filtration rate, with corresponding increases in the renal vascular resistance. The influence of these phenomena on the clinical outcome is considerable [8][9][10]. Thus, it is possible that this observed renal dysfunction is induced through the eNOS T-786C polymorphism and/or cardiopulmonary bypass in consequence to a decreased transcription rate and, presumably, with a reduction in NO production in the C-allele carrier.…”

“…Despite steady improvements in the results of cardiac surgery, there has been a trend in operating on higher risk patients, which leads to increased morbidity and mortality. The causes of renal dysfunction following cardiac surgery with cardiopulmonary bypass are poorly understood, but it is believed that they are multifactorial and usually attributed to the use of cardiopulmonary bypass, injury by exo-and endotoxins and pre-existing renal impairment [8][9][10]. Although many variables have been described that can identify the cardiac surgical patients who are at risk for renal dysfunction [2,5,7], significant unexplained variability in renal outcome still exists.…”

Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery

“…During cardiopulmonary bypass (CPB), blood is exposed to artificial surfaces, and is subjected to mechanical trauma, hemodilution, shear stress forces, and action of potent drugs [1][2][3][4][5][6]. Those could lead to activation of complements, cytokines, coagulofibrinolysis, and granulocytes [2][3][4][5][6][7].…”

“…Those could lead to activation of complements, cytokines, coagulofibrinolysis, and granulocytes [2][3][4][5][6][7]. Activated granulocytes release granular protein into the circulation [6].…”