Angus Derek C, Yang Lihong, Kong Lan, Kellum John A, Delude Russell L, Tracey Kevin J, Weissfeld Lisa
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, University of Pittsburgh, Pittsburgh, PA, USA.
Crit Care Med. 2007 Apr;35(4):1061-7. doi: 10.1097/01.CCM.0000259534.68873.2A.
High-mobility group box 1 (HMGB1) has been proposed as a late mediator of sepsis, but human data are sparse and conflicting. We describe plasma HMGB1 concentrations in humans with community-acquired pneumonia (CAP), the most common cause of severe sepsis, and test the hypotheses that HMGB1 levels are higher in CAP than healthy controls, higher in CAP with severe sepsis than CAP without severe sepsis, and higher in severe sepsis nonsurvivors than survivors.
Random, outcome-stratified sample from a prospective study of 1,895 subjects hospitalized with CAP.
Twenty-eight U.S. teaching and community hospitals.
There were 122 CAP subjects (43 never developed severe sepsis, 49 developed severe sepsis and survived hospitalization, and 30 developed severe sepsis and died) and 38 healthy controls.
None.
Median day of onset of severe sepsis was day of admission. HMGB1 was measured daily for the first week and analyzed using repeated-measures models with and without multivariable adjustment for baseline characteristics. HMGB1 concentrations were higher in CAP subjects compared with controls (median concentration on day of admission vs. controls, 190 vs. 0 ng/mL, p = .0001; 93.7% of all CAP measurements were elevated). HMGB1 remained elevated throughout the hospital course with no significant trend (p = .64) and did not differ between those with and without severe sepsis (p = .30). HMGB1 concentrations were higher in severe sepsis nonsurvivors than survivors (p = .001). HMGB1 concentrations remained elevated at discharge (median final HMGB1 measure, 176 ng/mL). Findings persisted in multivariable models and were robust to sensitivity analyses using alternative definitions of severe sepsis.
HMGB1 is elevated in almost all CAP subjects, and higher circulating HMGB1 is associated with mortality. But immunodetectable HMGB1 levels were also persistently elevated in those patients who fared well. Thus, additional work is needed to understand the biological activities of serum HMGB1 in sepsis.
高迁移率族蛋白B1（HMGB1）被认为是脓毒症的晚期介质，但相关人体数据稀少且存在矛盾。我们描述了社区获得性肺炎（CAP）患者（严重脓毒症最常见的病因）的血浆HMGB1浓度，并检验以下假设：CAP患者的HMGB1水平高于健康对照者；伴有严重脓毒症的CAP患者高于不伴有严重脓毒症的CAP患者；严重脓毒症非幸存者高于幸存者。
从一项对1895例因CAP住院患者的前瞻性研究中进行随机、按结局分层抽样。
美国28家教学医院和社区医院。
122例CAP患者（43例从未发生严重脓毒症，49例发生严重脓毒症且住院存活，30例发生严重脓毒症且死亡）以及38例健康对照者。
无。
严重脓毒症发病的中位时间为入院当天。在第一周每天测量HMGB1，并使用重复测量模型进行分析，对基线特征进行或不进行多变量调整。与对照组相比，CAP患者的HMGB1浓度更高（入院当天的中位浓度与对照组相比，分别为190 ng/mL和0 ng/mL，p = 0.0001；所有CAP测量值的93.7%升高）。在整个住院过程中，HMGB1一直处于升高状态，无明显趋势（p = 0.64），且在伴有和不伴有严重脓毒症的患者之间无差异（p = 0.30）。严重脓毒症非幸存者的HMGB1浓度高于幸存者（p = 0.001）。出院时HMGB1浓度仍处于升高状态（最终HMGB1测量值的中位值为176 ng/mL）。在多变量模型中这些发现依然存在，并且对使用严重脓毒症替代定义的敏感性分析具有稳健性。
几乎所有CAP患者的HMGB1均升高，循环中较高的HMGB1与死亡率相关。但在病情好转的患者中，免疫可检测的HMGB1水平也持续升高。因此，需要进一步开展工作以了解血清HMGB1在脓毒症中的生物学活性。
