Meduri G U, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K
Pulmonary and Critical Care Division, University of Tennessee Medical Center, Memphis, USA.
Chest. 1995 Apr;107(4):1062-73. doi: 10.1378/chest.107.4.1062.
Inflammatory cytokines have been related to the development of adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). We tested the hypothesis that unfavorable outcome in patients with ARDS is related to the presence of a persistent inflammatory response. For this purpose, we evaluated the behavior of inflammatory cytokines during progression of ARDS and the relationship of plasma inflammatory cytokines with clinical variables and outcome.
We prospectively studied 27 consecutive patients with severe medical ARDS. Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukins (ILs) 1 beta, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation. Subgroups of patients were identified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared for levels of plasma inflammatory cytokines on day 1 of ARDS and over time.
Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients with sepsis (86 vs 38%, p < 0.02). The mean initial plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 were significantly higher in nonsurvivors (p < 0.0001) and in those patients with sepsis (p < 0.0001). Plasma levels of IL-1 beta (p < 0.01) and IL-6 (p = 0.03) were more strongly associated with patient outcome than cause of ARDS (p = 0.8), lung injury score (LIS), APACHE II score, sepsis (p = 0.16), shock, or MODS score. Plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 remained significantly elevated over time (p < 0.0001) in those who died. Although it was the best early predictor of death (p < 0.001), plasma IL-2 > 200 pg/mL lost its usefulness after the first 48 h. A plasma IL-1 beta or IL-6 level > 400 pg/mL on any day in the first week of ARDS was associated with a low likelihood of survival.
Our findings indicate that unfavorable outcome in acute lung injury is related to the degree of inflammatory response at the onset and during the course of ARDS. Patients with higher plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 on day 1 of ARDS had persistent elevation of these inflammatory cytokines over time and died. Survivors had lesser elevations of plasma inflammatory cytokines on day 1 of ARDS and a rapid reduction over time. Plasma IL-1 beta and IL-6 levels were consistent and efficient predictors of outcome.
炎症细胞因子与成人呼吸窘迫综合征（ARDS）、休克及多器官功能障碍综合征（MODS）的发生发展相关。我们检验了这样一个假设，即ARDS患者不良预后与持续性炎症反应的存在有关。为此，我们评估了ARDS进展过程中炎症细胞因子的变化情况以及血浆炎症细胞因子与临床变量和预后的关系。
我们对27例连续的重症内科ARDS患者进行了前瞻性研究。在ARDS的第1、2、3、5、7、10和12天以及此后每隔三天患者接受机械通气时，采用酶联免疫吸附测定（ELISA）法检测血浆肿瘤坏死因子α（TNF-α）和白细胞介素（ILs）1β、2、4、6和8的水平。根据预后、ARDS病因、ARDS发生时是否存在脓毒症、休克和MODS对患者进行分组。比较各亚组在ARDS第1天及随时间变化的血浆炎症细胞因子水平。
27例患者中，13例入住重症监护病房后存活，14例死亡（死亡率为52%）。脓毒症患者的总体死亡率更高（86%对38%，p<0.02）。非存活者和脓毒症患者的TNF-α、IL-1β、IL-6和IL-8的初始血浆平均水平显著更高（p<0.0001）。与ARDS病因（p = 0.8）、肺损伤评分（LIS）、急性生理与慢性健康状况评分系统II（APACHE II）评分、脓毒症（p = 0.16）、休克或MODS评分相比，IL-1β（p<0.01）和IL-6（p = 0.03）的血浆水平与患者预后的相关性更强。死亡患者的TNF-α、IL-1β、IL-6和IL-8血浆水平随时间持续显著升高（p<0.0001）。虽然血浆IL-2>200 pg/mL是死亡的最佳早期预测指标（p<0.001），但在最初48小时后其预测价值丧失。ARDS第一周内任何一天血浆IL-1β或IL-6水平>400 pg/mL与生存可能性低相关。
我们的研究结果表明，急性肺损伤的不良预后与ARDS发病时及病程中的炎症反应程度有关。ARDS第1天血浆TNF-α、IL-1β、IL-6和IL-8水平较高的患者，这些炎症细胞因子随时间持续升高并死亡。存活者在ARDS第1天血浆炎症细胞因子升高幅度较小且随时间迅速下降。血浆IL-1β和IL-6水平是一致且有效的预后预测指标。
