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J Crit Care. 2014 Apr;29(2):312.e7-13. doi: 10.1016/j.jcrc.2013.10.008. Epub 2013 Oct 28.

The compromised inflammatory response to bacterial components after pediatric cardiac surgery is associated with cardiopulmonary bypass-suppressed Toll-like receptor signal transduction pathways.

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  • 1Institute for Pediatric Research, Soochow University Suzhou, China.
  • 2Department of Pediatric Cardiology, Affiliated Children's Hospital, Soochow University, Suzhou, China.
  • 3Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China.
  • 4Institute of Medical Biotechnology, Soochow University Suzhou, Suzhou, China.
  • 5Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland. Electronic address:
  • 6Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China. Electronic address:



Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery.


We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery.


Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)-stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α, interleukin (IL) 1β, IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κB p65, p38, and extracellular signal-regulated kinase 1/2.


These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.

© 2014.


Cardiopulmonary bypass; Congenital heart disease; Inflammatory responses; Intracellular signal pathways; TLR signaling

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