Callister M E, Burke-Gaffney A, Quinlan G J, Nicholson A G, Florio R, Nakamura H, Yodoi J, Evans T W
Unit of Critical Care, National Heart and Lung Institute Division, Imperial College Faculty of Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.
Thorax. 2006 Jun;61(6):521-7. doi: 10.1136/thx.2005.053041. Epub 2006 Apr 6.
Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult.
Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n=30) and healthy controls (n=18, plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores.
BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin.
Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.
急性肺损伤（ALI）及其严重表现形式急性呼吸窘迫综合征（ARDS）使多种严重内科和外科疾病复杂化。硫氧还蛋白是一种广泛存在的小分子硫醇蛋白，具有与ALI发病机制相关的氧化还原/炎症调节特性。因此，我们研究了ALI患者细胞外硫氧还蛋白水平是否升高，以及升高程度是否取决于诱发损伤的性质。
从ALI患者（n = 30）和健康对照者（血浆n = 18，支气管肺泡灌洗（BAL）液n = 14）采集BAL液和血浆样本。从另一组患者和对照者（n = 10）获取肺组织。通过酶联免疫吸附测定（ELISA）检测液体中的硫氧还蛋白，通过免疫组织化学检测组织中的硫氧还蛋白。通过ELISA测定白细胞介素（IL）-8水平。以急性生理与慢性健康状况评分系统II（APACHE II）和序贯器官衰竭评估（SOFA）评分评估疾病严重程度。
ALI患者BAL液中硫氧还蛋白水平高于对照组（中位数61.6 ng/ml（四分位间距34.9 - 132.9）对16.0 ng/ml（四分位间距8.9 - 25.1），p<0.0001）；血浆水平也显著更高。与对照组相比，ALI患者石蜡包埋肺组织切片在肺泡巨噬细胞和II型上皮细胞中硫氧还蛋白阳性染色更强。BAL液中硫氧还蛋白水平与BAL液中IL-8水平相关，但与疾病严重程度评分或死亡率无关。肺源性ALI患者BAL液中硫氧还蛋白、IL-8和中性粒细胞水平显著更高。
ALI患者，尤其是肺源性ALI患者，细胞外硫氧还蛋白水平升高，且与IL-8呈显著正相关。细胞外硫氧还蛋白水平可为ALI炎症提供有用指标。
