Serial circulating markers of inflammation in biliary atresia - Evolution of the post-operative inflammatory process
Serial circulating markers of inflammation in biliary atresia - Evolution of the post-operative inflammatory process
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DOI：
10.1002/hep.21701
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发表时间：
2007-07-01
期刊：
影响因子：
13.5
通讯作者：
Davenport, Mark
中科院分区：
文献类型：
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作者：
Narayanaswamy, Bornmayya;Gonde, Christopher;Davenport, Mark
胆道闭锁(BA)是一种同时累及肝内和肝外的阻塞性胆管病，伴有明显的炎症反应，包括肝脏内(主要)CD4+淋巴细胞和巨噬细胞的浸润。已知在门肠吻合术时，可溶性细胞黏附分子也会升高，推测这可能反映了肝内疾病。我们通过研究一组细胞黏附分子(可溶性细胞间黏附分子-1[sICAM-1]、可溶性血管细胞黏附分子-1[sVCAM-1])和可溶性促炎介质(T辅助因子1[白介素{IL}-2和干扰素-γ]和T辅助因子2[IL-4和IL-10])细胞因子和巨噬细胞标志物(肿瘤坏死因子[TNF]α和IL-18)来纵向研究这种可测量的炎症成分。所有粘附力的水平。门肠吻合术后6个月，分子和细胞因子(IL-10除外)呈进行性升高。这种反应是非极化的，但IL-2、TNFα和IL-18的水平尤其增加了100倍，但IL-10的水平仅略有上升。当促炎状态与预后相关时，我们发现，如果评估为黄疸清除，则分辨率较差，但对于将移植1年的患者，IL-2、干扰素-伽马、IL-4、IL-10、肿瘤坏死因子α和sICAM-1的值明显较高。通过对KP术后1个月sICAM-1水平的ROC曲线分析，以1,779 ng/ml为界值预测1年后是否需要移植，其特异度和敏感度分别为92%和87%。结论：BA早期的循环炎症过程是持续性的、进行性的，涉及一种非极化的T细胞、巨噬细胞和细胞黏附分子反应，而KP只能部分改善这种反应。
Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intra-and extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4+ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measurable inflammatory component longitudinally by studying a panel of cellular adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]) and soluble proinflammatory mediators (T helper 1 [interleukin {IL}-2 and interferon-gamma] and T helper 2 [IL-4 and IL-10]) cytokines and macrophage markers (tumor necrosis factor [TNF] alpha and IL-18) in 21 consecutive infants with BA post-Kasai portoenterostomy (KP). The levels of all adhesion. molecules and cytokines (except IL-10) increased progressively by 6 months post-portoenterostomy. The response was non-polarized but with 100-fold increases in IL-2, TNF alpha and IL-18 particularly but only modest elevations in IL-10. When proinflammatory profiles were related to outcome, we found poor discrimination if assessed as clearance of jaundice but markedly higher values for IL-2, interferon gamma, IL-4, IL-10, TNF alpha and sICAM-1 for those who would be transplanted by 1 year. Using ROC curve analysis for sICAM-1 levels at 1 month post-KP, a cutoff level of 1,779 ng/ml was determined to predict the need for transplantation at 1 year with 92% specificity and 87% sensitivity. Conclusion: The early circulating inflammatory process in BA is persistent, progressive and involves a non-polarized T cell, macrophage and cell adhesion molecule response only partially ameliorated by KP.