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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.

Author information

  • 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: jh.wang@ucc.ie.
  • 6Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China. Electronic address: wj196312@vip.163.com.

Abstract

PURPOSE:

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.

METHODS:

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

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

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

PMID:
24287173
[PubMed - indexed for MEDLINE]
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