title: The compromised inflammatory response to bacterial components after pediatric cardiac surgery is associated with cardiopulmonary bypass-suppressed Toll-like receptor signal transduction pathways.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute for Pediatric Research, Soochow University Suzhou, China.
authors.forename: Yi-ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: Department of Pediatric Cardiology, Affiliated Children's Hospital, Soochow University, Suzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China.
authors.forename: Shun-gen
authors.initials: SG
authors.lastname: Huang
authors.affiliation: Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China.
authors.forename: Yong-gen
authors.initials: YG
authors.lastname: Xu
authors.affiliation: Institute for Pediatric Research, Soochow University Suzhou, China.
authors.forename: Yun-yun
authors.initials: YY
authors.lastname: Xu
authors.affiliation: Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China.
authors.forename: Jian-yi
authors.initials: JY
authors.lastname: Liao
authors.affiliation: Institute for Pediatric Research, Soochow University Suzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Institute of Medical Biotechnology, Soochow University Suzhou, Suzhou, China.
authors.forename: Xue-guang
authors.initials: XG
authors.lastname: Zhang
authors.affiliation: Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland. Electronic address: jh.wang@ucc.ie.
authors.forename: Jiang Huai
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China. Electronic address: wj196312@vip.163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006321:Heart; D006330:Heart Defects, Congenital / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D008297:Male; D009000:Monocytes; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008074:Lipoproteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Cardiopulmonary bypass; Congenital heart disease; Inflammatory responses; Intracellular signal pathways; TLR signaling