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Alkaline phosphatase in pulmonary inflammation—a translational study in ventilated critically ill patients and rats
Intensive Care Medicine Experimental ( IF 2.8 ) Pub Date : 2020-12-01 , DOI: 10.1186/s40635-020-00335-x
Jenny Juschten , , Sarah A. Ingelse , Lieuwe D. J. Bos , Armand R. J. Girbes , Nicole P. Juffermans , Tom van der Poll , Marcus J. Schultz , Pieter Roel Tuinman

Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects. To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of recombinant AP on pulmonary inflammation in a well-established lung injury model in rats AP activity was determined and compared with levels of various inflammatory mediators in bronchoalveolar lavage fluid (BALF) samples obtained from critically ill patients within 2 days of start of invasive ventilation. The endpoints of this part of the study were the correlations between AP activity and markers of inflammation, i.e., interleukin (IL)-6 levels in BALF. In RccHan Wistar rats, lung injury was induced by intravenous administration of 10 mg/kg lipopolysaccharide, followed by ventilation with a high tidal volume for 4 h. Rats received either an intravenous bolus of 1500 IU/kg recombinant AP or normal saline 2 h after intravenous LPS administration, right before start of ventilation. Endpoints of this part of the study were pulmonary levels of markers of inflammation, including IL-6, and markers of endothelial and epithelial dysfunction. BALF was collected from 83 patients; 10 patients had mild ARDS, and 15 had moderate to severe ARDS. AP activity correlated well with levels of IL-6 (r = 0.70), as well as with levels of other inflammatory mediators. Pulmonary AP activity between patients with and without ARDS was comparable (0.33 [0.14–1.20] vs 0.55 [0.21–1.42] U/L; p = 0.37). Animals with acute lung injury had markedly elevated pulmonary AP activity compared to healthy controls (2.58 [2.18–3.59] vs 1.01 [0.80–1.46] U/L; p < 0.01). Intravenous administration of recombinant AP did neither affect pulmonary inflammation nor endothelial and epithelial dysfunction. In ventilated critically ill patients, pulmonary AP activity correlates well with markers of pulmonary inflammation, such as IL-6 and IL-8. In animals with lung injury, pulmonary AP activity is elevated. Administration of recombinant AP does not alter pulmonary inflammation and endothelial or epithelial dysfunction in the acute phase of a murine lung injury model.

中文翻译:

肺部炎症中的碱性磷酸酶——对通气危重患者和大鼠的转化研究

碱性磷酸酶 (AP) 是一种去磷酸化酶,参与各种生理过程,并已被证明具有抗炎作用。确定患有或不患有急性呼吸窘迫综合征 (ARDS) 的有创通气危重患者的肺 AP 活性与炎症标志物之间的相关性,并在完善的肺损伤模型中研究重组 AP 对肺部炎症的影响测定大鼠 AP 活性,并与从有创通气开始 2 天内从危重患者获得的支气管肺泡灌洗液 (BALF) 样本中的各种炎症介质的水平进行比较。这部分研究的终点是 AP 活性与炎症标志物之间的相关性,即,BALF 中的白细胞介素 (IL)-6 水平。在 RccHan Wistar 大鼠中,通过静脉注射 10 mg/kg 脂多糖诱导肺损伤,然后以高潮气量通气 4 h。在静脉注射 LPS 后 2 小时,就在通气开始前,大鼠接受了 1500 IU/kg 重组 AP 的静脉推注或生理盐水。这部分研究的终点是炎症标志物的肺部水平,包括 IL-6,以及内皮和上皮功能障碍的标志物。BALF 收集自 83 名患者;10 名患者患有轻度 ARDS,15 名患者患有中度至重度 ARDS。AP 活性与 IL-6 的水平 (r = 0.70) 以及其他炎症介质的水平密切相关。患有和未患有 ARDS 的患者的肺 AP 活动具有可比性(0.33 [0.14–1.20] vs 0.55 [0.21–1.42] U/L;p = 0.37)。与健康对照相比,急性肺损伤动物的肺 AP 活性显着升高(2.58 [2.18–3.59] 对 1.01 [0.80–1.46] U/L;p < 0.01)。重组 AP 的静脉给药既不影响肺部炎症也不影响内皮和上皮功能障碍。在通气的危重患者中,肺 AP 活性与肺部炎症的标志物(如 IL-6 和 IL-8)密切相关。在有肺损伤的动物中,肺 AP 活性升高。在鼠肺损伤模型的急性期,重组 AP 的给药不会改变肺部炎症和内皮或上皮功能障碍。重组 AP 的静脉给药既不影响肺部炎症也不影响内皮和上皮功能障碍。在通气的危重患者中,肺 AP 活性与肺部炎症的标志物(如 IL-6 和 IL-8)密切相关。在有肺损伤的动物中,肺 AP 活性升高。在鼠肺损伤模型的急性期,重组 AP 的给药不会改变肺部炎症和内皮或上皮功能障碍。重组 AP 的静脉给药既不影响肺部炎症也不影响内皮和上皮功能障碍。在通气的危重患者中,肺 AP 活性与肺部炎症的标志物(如 IL-6 和 IL-8)密切相关。在有肺损伤的动物中,肺 AP 活性升高。在鼠肺损伤模型的急性期,重组 AP 的给药不会改变肺部炎症和内皮或上皮功能障碍。
更新日期:2020-12-01
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