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

Cytokine. 2019 Oct;122:154018. doi: 10.1016/j.cyto.2017.03.017. Epub 2017 Apr 12.

Abstract

Background: Corrective 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.

Objectives: The aim of this prospective study was to analyze immunodepression after pediatric cardiopulmonary bypass and to differentiate the effects of monocytic anergy on postoperative outcome.

Methods: In 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.

Results: The 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).

Conclusion: Cardiosurgery 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.

Keywords: Cardiopulmonary bypass; Cytokines; Immunodepression; Monocyte function; Monocytic anergy; Pediatric cardiac surgery; Surgical trauma.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiopulmonary Bypass / adverse effects*
  • Chemokine CCL2 / blood
  • Child, Preschool
  • Cytokines / blood*
  • Female
  • Humans
  • Infant
  • Inflammation / etiology*
  • Inflammation / immunology
  • Interferon-gamma / blood
  • Interleukin-1 Receptor Accessory Protein / blood
  • Interleukin-10 / metabolism
  • Interleukin-12 / blood
  • Interleukin-17 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Lipopolysaccharides / immunology
  • Male
  • Monocytes / immunology*
  • Postoperative Complications
  • Prospective Studies
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Cytokines
  • IL10 protein, human
  • IL1B protein, human
  • IL1RAP protein, human
  • IL6 protein, human
  • Interleukin-1 Receptor Accessory Protein
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma