Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery—A Prospective Cohort Study

Abstract

Interleukin-6 (IL-6) can cause pro- and anti-inflammatory effects via different signaling pathways. This prospective study investigated the perioperative kinetics of IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in elective patients undergoing cardiopulmonary bypass (CPB). IL-6, sIL-6R, and sgp130 were measured simultaneously and consecutively at 19 timepoints until the 10th postoperative day (POD). The proportion of pro- and anti-inflammatory pathways were determined by calculating sIL-6R/IL-6 and sIL-6R/sgp130 ratios. We analyzed 93 patients. IL-6 increased during surgery with reaching a plateau two hours after CPB and peaking on POD 1 (188.5 pg mL−1 (IQR, 126.6; 309.2)). sIL-6R decreased at the beginning of the surgical procedure, reaching a nadir level on POD 2 (26,311 pg mL−1 (IQR, 22,222; 33,606)). sgp130 dropped immediately after CPB initiation (0.13 ng mL−1 (IQR, 0.12; 0.15)), followed by a continuous recovery until POD10. The sIL-6R/IL-6 ratio decreased substantially at the beginning of the procedure, reaching a nadir on POD 1 (149.7 (IQR, 82.4; 237.4)), while the sIL-6R/sgp130 ratio increased simultaneously until 6 h post CPB (0.219 (IQR 0.18; 0.27)). In conclusion, IL-6 exhibited high inter-individual variability reflecting an inhomogeneous inflammatory response. Pro-inflammatory effects and overwhelming inflammation were rare and predominantly anti-inflammatory effects were found.

Impact of CytoSorb® on interleukin-6 in cardiac surgery

“…The fact that the half-life of IL-6 lies within minutes, suggests that once the causative trigger is eliminated, IL-6 levels should decrease rapidly, i.e., after surgery, remaining elevated only in cases of prolonged immune answer e.g., sepsis ( 17 ). Albeit the IL-6 course, with an elevation about 6 h after surgery, corresponds to our data, we found in contrast prolonged elevated IL-6 levels postoperatively with a peak on the first POD, in line with Puchinger et al ( 18 ) However, HA consistently had no significant effect on systemic inflammatory response or clinical outcome, respectively, supporting our results.…”

Cardiac surgery elicits pericardial inflammatory responses that are distinct compared with postcardiopulmonary bypass systemic inflammation

“…To date, the systemic post-CPB inflammatory response has been extensively studied. 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 It is believed that CPB and ischemia–reperfusion injury play an important role in activating systemic inflammatory cascades. However, the inflammatory processes that occur in the pericardial space after surgery have been poorly characterized and there is a paucity of data comparing the local inflammatory response to the systemic inflammation that occurs in these patients.…”

“…Moreover, several studies demonstrate that the cardiopulmonary bypass (CPB) machine elicits a robust systemic inflammatory response. 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 This inflammatory response, which is characterized by immune-mediated pathways, such as activation of the complement system, is associated with adverse clinical outcomes, including acute kidney injury, lung injury, and neurocognitive disorders. 16 , 17 , 18 …”

Effects of multimodal low-opioid anesthesia protocol during on-pump coronary artery bypass grafting: a prospective cohort study

“…Further, contact of blood components with the surface of the extracorporeal circuits, reperfusion injuries, endotoxemia, and surgical trauma are among the processes that can activate the pro-inflammatory system and cytokine release, mainly interleukin-6 (IL-6) during on-pump CABG [ 6 , 7 ]. IL-6 is a widely discussed biomarker in conjunction with extracorporeal circulation and inflammation during cardiac surgical interventions [ 8 ]. Recent investigations confirmed the interaction between the immune system and the opioids, both in terms of stimulatory and suppressive effects, but this is still not clearly understood [ 9 ].…”