Interleukin 12 and interferon-gamma synthetic deficiency is associated with dendritic cell cytopenia after cardiac surgery.
Interleukin 12 and interferon-gamma synthetic deficiency is associated with dendritic cell cytopenia after cardiac surgery.
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白细胞介素 12 和干扰素 γ 合成缺陷与心脏手术后树突状细胞血细胞减少有关。
DOI：
10.1097/01.shk.0000167110.73129.a8
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Heinzel,FrederickP
中科院分区：
文献类型：
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作者：
Yadavalli,GopalaK;Chien,JasonW;Wener,KennethM;Devecchio,JenniferL;Gupta,Sameer;Salata,RobertA;Lee,JaiH;Caldeira,Christiano;Auletta,JefferyJ;Heinzel,FrederickP
创伤性或炎症性损伤与单核细胞失活和促炎细胞因子合成受损有关。我们进行了一项前瞻性观察性研究，以测试心脏手术是否会额外损害树突状细胞和自然杀伤细胞（NK）功能，这些细胞负责对细菌或toll样受体激动剂的先天免疫产生白细胞介素(IL)-12依赖性干扰素(IFN)-γ。在麻醉诱导前和术后24 h采集血样。手术后全血培养中lps和固定金黄色葡萄球菌诱导的IFNγ合成降低到术前值的5% （P< 0.001）。IL-12 p70（先天免疫应答中IFNγ的关键诱导剂）的产生减少到术前样品的30% （P= 0.013）。正常血液中已知的il - 12p70来源的循环CD11c+、DR+髓样树突状细胞（DC）下降到手术前数量的约25% （P= 0.004）。正常外周血单核细胞（PBMC）中CD11c+而非CD14+的实验缺失同样使金黄色葡萄球菌Cowan 1 （SAC）失能，诱导il - 12p70和IFNγ的产生。与sacc诱导的CD56+ NK细胞和NK- t细胞中IFNγ的表达一致，CD56缺失减少了正常全血中IFNγ的产生。然而，术后血液中IL-12 p70、IL-18、IL-15和IL-23的补充未能恢复手术前的IFNγ合成水平（P< 0.05）。我们得出结论，大手术后DC细胞减少足以解释术后IL-12 p70和IFNγ合成缺陷。此外，术后血液对IFNγ诱导细胞因子的反应降低，进一步导致IFNγ不足。大手术后DC细胞减少的新发现可能预示着缺乏这种强大的辅助细胞群提供的其他免疫功能。
Traumatic or inflammatory injury associates with deactivation of monocytes and impaired synthesis of proinflammatory cytokines. We conducted a prospective, observational study to test whether cardiac surgery additionally impaired dendritic and natural killer (NK) cell functions responsible for innate immune production of interleukin (IL)-12-dependent interferon (IFN)-γ in response to bacteria or toll-like receptor agonists. Blood samples were taken just before induction of anesthesia and 24 h postoperatively. LPS-and fixed Staphylococcus aureus-inducible IFNγ synthesis in whole blood culture after surgery was reduced to 5% of preoperative values (P< 0.001). Production of IL-12 p70, a critical inducer of IFNγ in the innate immune response, was reduced to 30% of that produced by preoperative samples (P= 0.013). Circulating CD11c+, DR+ myeloid dendritic cells (DC) that are known sources of IL-12 p70 in normal blood, declined to approximately 25% of presurgical numbers (P= 0.004). Experimental depletion of CD11c+, but not CD14+, cells from normal peripheral blood mononuclear cell (PBMC) similarly disabled Staphylococcus aureus Cowan 1 (SAC)-induced production of IL-12 p70 and IFNγ. Consistent with SAC-induced IFNγ expression in CD56+ NK and NK-T cells, CD56 depletion ablated IFNγ production in normal whole blood. However, repletion of IL-12 p70, IL-18, IL-15, and IL-23 in postoperative blood failed to restore presurgical levels of IFNγ synthesis (P< 0.05). We conclude that DC cytopenia after major surgery is sufficient to explain postoperative IL-12 p70 and IFNγ synthetic deficiency. In addition, postoperative blood became hyporesponsive to IFNγ-inducing cytokines as a further contribution to IFNγ insufficiency. The novel finding of DC cytopenia after major surgery may portend a lack of other immunologic functions provided by this potent accessory cell population.