High Postoperative Blood Levels of Macrophage Migration Inhibitory Factor Are Associated with Less Organ Dysfunction in Patients after Cardiac Surgery

Abstract

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that exerts protective effects during myocardial ischemia/reperfusion injury. We hypothesized that elevated MIF levels in the early postoperative time course might be inversely associated with postoperative organ dysfunction as assessed by the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) score in patients after cardiac surgery. A total of 52 cardiac surgical patients (mean age [± SD] 67 ± 10 years; EuroScore: 7 [2-11]) were enrolled in this monocenter, prospective observational study. Serum levels of MIF and clinical data were obtained after induction of anesthesia, at admission to the intensive care unit (ICU), 4 h after admission and at the first and second postoperative day. To characterize the magnitude of MIF release, we compared blood levels of samples from cardiac surgical patients with those obtained from healthy volunteers. We assessed patient outcomes using the SAPS II at postoperative d 1 and SOFA score for the first 3 d of the eventual ICU stay. Compared to healthy volunteers, patients had already exhibited elevated MIF levels prior to surgery (64 ± 50 versus 13 ± 17 ng/mL; p < 0.05). At admission to the ICU, MIF levels reached peak values (107 ± 95 ng/mL; p < 0.01 versus baseline) that decreased throughout the observation period and had already reached preoperative values 4 h later. Postoperative MIF values were inversely correlated with SAPS II and SOFA scores during the early postoperative stay. Moreover, MIF values on postoperative d 1 were related to the calculated cardiac power index (r = 0.420, p < 0.05). Elevated postoperative MIF levels are inversely correlated with organ dysfunction in patients after cardiac surgery.

Graft‐derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation

“…We found a 1000‐fold greater MIF concentration in the liver graft effluent than in recipients’ serum before and after reperfusion, suggesting that the human liver graft is a major source of MIF. Previous studies reported maximal MIF concentrations between 0.1 and 3.2 μg/mL in human blood . The marked release of MIF during human liver graft preservation observed in our study might trigger an inflammatory response within the liver graft.…”

The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery

“…Comparable to sepsis, cardiac surgery with use of cardiopulmonary bypass (CPB) is associated with systemic oxidative stress and hemodynamic changes, resulting in a transiently decreased perfusion of organs, including the kidney. We and others have demonstrated that MIF is elevated during the perioperative inflammatory response after cardiac surgery (20,21). Several studies have revealed cardioprotective effects of MIF in the setting of acute myocardial I/R injury (20,22,23), but the functional role and clinical relevance of MIF in the development of postoperative AKI remain unknown.…”

“…MIF was shown to have antioxidant properties (20)(21)(22)(23)(24), potentially by its thiol-protein oxidoreductase (TPOR) activity. Here, we tested the hypothesis that MIF might be a protective factor limiting AKI through cytoprotective and antioxidative effects, using a comprehen-sive combined clinical and experimental approach including the stateof-the-art assessment of apoptosis, necroptosis, and ferroptosis.…”

A randomized trial of remote ischemic preconditioning and control treatment for cardioprotection in sevoflurane-anesthetized CABG patients

“…However, we did not observe any differences in serum MIF levels between control and RIPC treated patient after RIPC, supporting the other observations of no effects of RIPC. It should be noted however, that many values (25) were below the detection limit, and lower than observed in other studies with CABG patients [47, 48]. Therefore, these results should be interpreted with care.…”

“…Ischemia caused a release of MIF from the heart, which has been shown to be cardioprotective by regulation of AMPK signaling, inhibition of pro-apoptotic cascades and reducing oxidative stress [45–47]. In CABG patients a perioperative increase in MIF was associated with enhanced antioxidant capacity and reduced organ dysfunction after cardiac surgery [47, 48]. We hypothesized that RIPC can increase MIF.…”