Immunodepression after CPB: Cytokine dynamics and clinics after pediatric cardiac surgery – A prospective trial

Abstract

BackgroundCorrective surgery for congenital heart defects is known to trigger a severe immune reaction. There has been extensive research on the effects of inflammation after cardiopulmonary bypass (CPB). Interestingly, monocytes are observed to be non-responsive to stimulation with lipopolysaccharide (LPS) under these conditions, indicating a state of immunodepression, which lays the ground for second hit infections after cardiosurgery with CPB. ObjectivesThe aim of this prospective study was to analyze immunodepression after pediatric cardiopulmonary bypass and to differentiate the effects of monocytic anergy on postoperative outcome. MethodsIn a prospective trial, we quantified the immune responses in 20 pediatric patients (median age 4.9months, range 2.3–38.2months; median weight 7.2kg, range 5.2–11.7kg) with congenital ventricular septal defect undergoing heart surgery with CPB. Ex vivo LPS-induced protein expression of IFN-γ, IL-1β, IL-1Ra, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and MCP-1 was measured before (T1), immediately after (T2) and 4h after (T3) cardiopulmonary bypass surgery using Luminex technology. ResultsThe innate immune system responds to CPB with an almost complete depression of monocytic function. Inflammatory IL-12, TNF-α, IL-1β, IL-6, IL-8 and IFN-y are completely suppressed. IL-10, IL-1Ra and MCP-1 are still produced during suppression with IL-1Ra being overly secreted during reversion. Suppression of TNF-α expression after LPS-stimulation correlates closely with longer mechanical ventilation time (r=−0.619, p=0.004). ConclusionCardiosurgery with CPB causes a state of immunodepression making pediatric patients more vulnerable to second hit infections. MCP-1, IL-10, and IL-1Ra play an important role in monocyte recovery, eventually permitting new therapeutic options for controlling immunodepression and inflammation. Standardized glucocorticoid therapy should be evaluated carefully for each individual patient.