Reindl-Schwaighofer Roman, Eskandary Farsad, Bartko Johann, Heinzel Andreas, Jilma Bernd, Hecking Manfred, Schoergenhofer Christian
Department of Nephrology and Dialysis, Division of Medicine III, Medical University of Vienna, Vienna, Austria.
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Front Med (Lausanne). 2022 Mar 2;9:856891. doi: 10.3389/fmed.2022.856891. eCollection 2022.
The assessment of systemic corticosteroid effects on intrapulmonary disease biomarkers is challenging. This retrospective evaluation of a human endotoxemia model quantified ACE2 and fibrin degradation product (FDP) concentrations in bronchoalveolar lavage fluid (BALF) samples from a randomized, double-blind, placebo-controlled study (NCT01714427). Twenty-four healthy volunteers received either 2 × 40 mg intravenous dexamethasone or placebo. These doses were administered 12 h apart prior to bronchoscopy-guided intrabronchial lipopolysaccharide (LPS) stimulation (control: saline into the contralateral lung segment). We quantified ACE2 concentration, the Angiotensin-II-to-Angiotensin-1-7 conversion rate as well as FDP in BALF 6 h after LPS instillation. In placebo-treated subjects, LPS instillation increased ACE2 concentrations compared to unstimulated lung segments [1,481 (IQR: 736-1,965) vs. 546 (413-988) pg/mL; = 0.016]. Dexamethasone abolished the increase in ACE2 concentrations (p=0.13). Accordingly, LPS instillation increased the Angiotensin-II-to-Angiotensin-1-7 conversion capacity significantly in the placebo cohort, indicating increased enzymatic activity ( = 0.012). FDP increased following LPS-instillation [8.9 (2.7-12.2) vs. 6.6 (0.9-9.6) ng/mL, = 0.025] in the placebo group, while dexamethasone caused a shut-down of fibrinolysis in both lung segments. LPS instillation increased ACE2 concentration, its enzymatic activity and FDP, which was mitigated by systemic dexamethasone treatment. Our results strengthen previously published findings regarding the efficiency of corticosteroids for the treatment of COVID-19-induced acute lung injury.
评估全身用皮质类固醇对肺内疾病生物标志物的影响具有挑战性。本研究对人类内毒素血症模型进行回顾性评估，对一项随机、双盲、安慰剂对照研究（NCT01714427）的支气管肺泡灌洗（BALF）样本中的血管紧张素转换酶2（ACE2）和纤维蛋白降解产物（FDP）浓度进行了量化。24名健康志愿者接受了2×40mg静脉注射地塞米松或安慰剂。在支气管镜引导下进行支气管内脂多糖（LPS）刺激（对照：向对侧肺段注入生理盐水）前12小时，间隔给药。在LPS滴注后6小时，我们对BALF中的ACE2浓度、血管紧张素II向血管紧张素1-7的转化率以及FDP进行了量化。在安慰剂治疗的受试者中，与未受刺激的肺段相比，LPS滴注使ACE2浓度升高[1,481（四分位间距：736-1,965）对546（413-988）pg/mL；P = 0.016]。地塞米松消除了ACE2浓度的升高（P=0.13）。因此，在安慰剂组中，LPS滴注显著提高了血管紧张素II向血管紧张素1-7的转化能力，表明酶活性增加（P = 0.012）。在安慰剂组中，LPS滴注后FDP升高[8.9（2.7-12.2）对6.6（0.9-9.6）ng/mL，P = 0.025]，而地塞米松导致两个肺段的纤维蛋白溶解停止。LPS滴注增加了ACE2浓度、其酶活性和FDP，而全身用地塞米松治疗可减轻这些变化。我们的结果强化了先前发表的关于皮质类固醇治疗COVID-19诱导的急性肺损伤疗效的研究结果。
