Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany.
Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; Department of Pediatrics, Division of Cardiology, Charité-Universitätsmedizin, Berlin, Germany.
Cytokine. 2019 Oct;122:154018. doi: 10.1016/j.cyto.2017.03.017. Epub 2017 Apr 12.
Corrective surgery for congenital heart defects is known to trigger a severe immune reaction. There has been extensive research on the effects of inflammation after cardiopulmonary bypass (CPB). Interestingly, monocytes are observed to be non-responsive to stimulation with lipopolysaccharide (LPS) under these conditions, indicating a state of immunodepression, which lays the ground for second hit infections after cardiosurgery with CPB.
The aim of this prospective study was to analyze immunodepression after pediatric cardiopulmonary bypass and to differentiate the effects of monocytic anergy on postoperative outcome.
In a prospective trial, we quantified the immune responses in 20 pediatric patients (median age 4.9months, range 2.3-38.2months; median weight 7.2kg, range 5.2-11.7kg) with congenital ventricular septal defect undergoing heart surgery with CPB. Ex vivo LPS-induced protein expression of IFN-γ, IL-1β, IL-1Ra, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and MCP-1 was measured before (T1), immediately after (T2) and 4h after (T3) cardiopulmonary bypass surgery using Luminex technology.
The innate immune system responds to CPB with an almost complete depression of monocytic function. Inflammatory IL-12, TNF-α, IL-1β, IL-6, IL-8 and IFN-y are completely suppressed. IL-10, IL-1Ra and MCP-1 are still produced during suppression with IL-1Ra being overly secreted during reversion. Suppression of TNF-α expression after LPS-stimulation correlates closely with longer mechanical ventilation time (r=-0.619, p=0.004).
Cardiosurgery with CPB causes a state of immunodepression making pediatric patients more vulnerable to second hit infections. MCP-1, IL-10, and IL-1Ra play an important role in monocyte recovery, eventually permitting new therapeutic options for controlling immunodepression and inflammation. Standardized glucocorticoid therapy should be evaluated carefully for each individual patient.
众所周知，先天性心脏缺陷的矫正手术会引发严重的免疫反应。已有大量研究关注体外循环（CPB）后炎症的影响。有趣的是，在这些条件下，单核细胞对脂多糖（LPS）的刺激无反应，表明存在免疫抑制状态，这为 CPB 心脏手术后的二次打击感染奠定了基础。
本前瞻性研究旨在分析小儿体外循环后的免疫抑制，并区分单核细胞无反应对术后结果的影响。
在一项前瞻性试验中，我们对 20 名接受 CPB 心脏手术的先天性室间隔缺损小儿患者（中位年龄 4.9 个月，范围 2.3-38.2 个月；中位体重 7.2kg，范围 5.2-11.7kg）的免疫反应进行了量化。使用 Luminex 技术，在体外循环手术前（T1）、手术即刻（T2）和术后 4 小时（T3）测量 IFN-γ、IL-1β、IL-1Ra、IL-6、IL-8、IL-10、IL-12、IL-17、TNF-α和 MCP-1 的蛋白表达。
固有免疫系统对 CPB 反应强烈，单核细胞功能几乎完全受到抑制。炎性细胞因子 IL-12、TNF-α、IL-1β、IL-6、IL-8 和 IFN-y 完全受到抑制。IL-10、IL-1Ra 和 MCP-1 在抑制过程中仍有产生，而在恢复过程中 IL-1Ra 过度分泌。LPS 刺激后 TNF-α表达的抑制与机械通气时间延长密切相关（r=-0.619，p=0.004）。
CPB 心脏手术导致免疫抑制状态，使小儿患者更容易受到二次打击感染。MCP-1、IL-10 和 IL-1Ra 在单核细胞恢复中发挥重要作用，最终为控制免疫抑制和炎症提供新的治疗选择。应仔细评估每个患者的标准化糖皮质激素治疗。
