The compromised inflammatory response to bacterial components after pediatric cardiac surgery is associated with cardiopulmonary bypass-suppressed Toll-like receptor signal transduction pathways
| Autor: | Yunyun Xu, Jianyi Liao, Jie Huang, Xueguang Zhang, Jian Wang, Yong-gen Xu, Shun-gen Huang, Jiang Huai Wang, Yi-Ping Li, Xing Feng |
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| Rok vydání: | 2013 |
| Předmět: |
Heart Defects
Congenital Lipopolysaccharides Male Lipopolysaccharide CD14 Lipoproteins Interleukin-1beta Lipopolysaccharide Receptors Critical Care and Intensive Care Medicine Monocytes law.invention Proinflammatory cytokine chemistry.chemical_compound law Cardiopulmonary bypass Medicine Humans Toll-like receptor Cardiopulmonary Bypass business.industry Interleukin-6 Tumor Necrosis Factor-alpha Interleukin-8 Toll-Like Receptors Infant Heart Systemic Inflammatory Response Syndrome Toll-Like Receptor 2 Interleukin-10 Toll-Like Receptor 4 TLR2 chemistry Immunology TLR4 Cytokines Female Signal transduction business Signal Transduction |
| Zdroj: | Journal of critical care. 29(2) |
| ISSN: | 1557-8615 |
| Popis: | 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) 1 β , 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 κ B 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. |
| Databáze: | OpenAIRE |
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