Kellum John A, Kong Lan, Fink Mitchell P, Weissfeld Lisa A, Yealy Donald M, Pinsky Michael R, Fine Jonathan, Krichevsky Alexander, Delude Russell L, Angus Derek C
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 604 Scaife Hall, 3550 Terrace St, Pittsburgh, PA15261, USA.
Arch Intern Med. 2007;167(15):1655-63. doi: 10.1001/archinte.167.15.1655.
Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of proinflammatory and anti-inflammatory markers, are associated with severe sepsis and death.
This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality.
A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8-39.0) (P<.001).
The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest when both proinflammatory and anti-inflammatory cytokine levels are high.
严重脓毒症很常见且常常致命，社区获得性肺炎（CAP）是其主要病因。尽管严重脓毒症常被归因于失控和失衡的炎症反应，但缺乏来自各种感染综合征患者的证据。在本研究中，我们描述了肺炎患者的全身细胞因子反应，并确定特定模式，包括促炎和抗炎标志物的平衡，是否与严重脓毒症及死亡相关。
这是一项对1886名通过美国28家学术和社区医院急诊科因CAP住院的患者进行的队列研究。按照国际共识会议标准，我们将严重脓毒症定义为并发新发器官功能障碍的CAP。在第一周每天测量血浆肿瘤坏死因子、IL-6（白细胞介素6）和IL-10水平，此后每周测量一次。我们的主要结局指标是严重脓毒症和90天死亡率。
共有583例患者发生严重脓毒症（31%），其中149例死亡（26%）。82%的CAP患者出现全身细胞因子水平升高。平均细胞因子浓度在就诊时最高，在最初几天迅速下降，但在第一周内一直保持升高，超过感染临床症状消退时间。致命性严重脓毒症患者的细胞因子水平最高，无严重脓毒症的CAP患者的细胞因子水平最低。失衡（高/低）细胞因子模式不常见（4.6%），且与生存率降低无关。死亡风险最高的是促炎IL-6和抗炎IL-10细胞因子活性均高的患者（风险比，20.5；95%置信区间，10.8 - 39.0）（P <.001）。
肺炎患者的循环细胞因子反应具有异质性，在就诊后持续超过一周，发生和未发生严重脓毒症的患者之间有相当大的重叠。失衡激活不常见，促炎和抗炎细胞因子水平均高时死亡率最高。
