Alterations of the cytokine network in patients undergoing cardiopulmonary bypass

Abstract

Cardiovascular surgery using extracorporeal circulation causes a systemic inflammatory response which often results in severe organ dysfunction and increased postoperative mortality. Advances in knowledge about the interactions of cytokines involved in the response to cardiopulmonary bypass (CPB) may improve the outcome of patients undergoing cardiac surgery. The purpose of our study was to investigate the fluctuations in cytokine production, during and after CPB. In 24 patients undergoing elective coronary artery bypass grafting, plasma levels of interleukins IL-2, IL-6, IL-10 and IL-12, soluble IL-2-receptor (sIL-2R), and transforming growth factor-beta (TGF-beta) were measured at eight time points before, during and after CPB, using a standardized enzyme-linked immunosorbant assay technique. There was a significant increase in plasma levels of IL-10, IL-6 and TGF-beta after weaning off CPB. The IL-2 plasma levels decreased after the onset of CPB until 24 h postoperatively (p < 0.05). Concentrations of sIL-2R decreased 20 min after the start of CPB until the end of the operation (p < 0.05). In the postoperative course, sIL-2R levels increased, with peak values 48 h after the end of the surgical procedure. The IL-12 levels decreased after weaning off CPB (p < 0.05) until 6 h postoperatively. The results of our study demonstrate an intraoperative-predominant immunosuppression, followed by an early postoperative immunological activation, combined with a distinct acute phase response.

Interleukin-6 Gene −174G>C and −572G>C Promoter Polymorphisms Are Strong Predictors of Plasma Interleukin-6 Levels After Coronary Artery Bypass Surgery

“…These evoke a marked inflammatory response, inducing the release of proinflammatory cytokines, such as IL-6. [31][32][33][34][35][36] We describe for the first time the effect of 3 common genetic polymorphisms found in the IL-6 gene promoter on basal and inflammatory IL-6 levels in patients undergoing elective CABG. The use of an in vivo acute inflammatory model, such as bypass surgery, allows more realistic assessment of genotype function than in vitro experimentation and may reflect changes that are clinically relevant.…”

“…[31][32][33][34][35][36] In the early phase, a severe acute inflammatory response occurs, resulting in a peak IL-6 response at the 6-hour time point. 32,34 -36 Evidently, a variety of different stimuli (such as sternal incision and general anesthesia) might be thought to play a role in the genesis of this response.…”

“…CABG is a well-characterized inflammatory stimulus that causes a substantial rise in circulating IL-6 levels that peak 6 hours after patients are placed on cardiopulmonary bypass (CPB). [31][32][33][34][35][36] Although a variety of different factors might act as potential stimuli to this inflammatory response, available evidence supports an important role for the process of CPB itself, 34 and accordingly, CABG provides a fairly uniform stimulus for IL-6 production. Therefore, the influence of IL-6 genotype on this more homogeneous acute inflammatory stimulus was the primary focus of the present study.…”

Cardiac Surgery and Allogeneic Blood Transfusions

“…The production and release of the inflammatory mediators could be predictive in the development of postoperative complications after cardiac surgery. In one study (Sablotzki et al, 1997) the cytokine pattern were measured up to 48 hours after CABG surgery in 24 patients who all recovered uneventfully. After the start of bypass, soluble IL-2 receptor, IL-2 and IL-12 decrease and incompletely restore themselves, respectively 6-48 hours after surgery.…”

Macrophage Migration Inhibitory Factor in Pediatric Patients Undergoing Surgery for Congenital Heart Repair

“…Several factors can trigger the systemic inflammatory response, including cardiac ischemiareperfusion injury, activation of leukocytes with bioactive surfaces, endotoxemia, use of cardioplegia, and surgical trauma (3). This inflammatory process involves the activation of lymphocytes, monocytes/macrophages, endothelial cells, and cardiac myocytes that can express and secrete proinflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, and IL-8, and anti-inflammatory cytokines [IL-4, IL-10, transforming growth factor β (TGFβ)] (4,5).…”