Heagy W, Hansen C, Nieman K, Cohen M, Richardson C, Rodriguez J L, West M A
Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis Medical Research Foundation, 55415, USA.
Shock. 2000 Sep;14(3):271-6; discussion 276-7. doi: 10.1097/00024382-200014030-00005.
Currently, there is no reliable diagnostic test to identify septic intensive care unit (ICU) patients. We initiated studies to test the hypothesis that in sepsis, the in vivo exposure to endotoxin is detectable by the ex vivo analysis of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production. We obtained heparinized whole blood (WB) from 58 ICU patients and 14 healthy controls. The samples were incubated +/-10 ng/mL of LPS at 37 degrees C for 3 h. Plasma TNF levels were measured using enzyme-linked immunoassay (mean +/- standard error of the mean). Clinical data, including ICU length of stay (LOS), ventilator days (VentD), WBC, and positive cultures (Clt+), were obtained retrospectively. A wide range of LPS-stimulated WB TNF production (pg/mL) was observed in ICU patients (4481+/-469) and controls (6706+/-715). Patients were stratified into quartiles (I-IV) on the basis of the distribution of plotted LPS-stimulated TNF values (pg/mL). Patients in quartile I (N = 14) had significantly lower TNF production (< 2000 pg/mL, P < 0.05) and required increased VentD (16 vs. 10 days, P < 0.05) compared to quartiles II-IV (N = 44). Patients in quartile I also had a higher incidence of infection (79 vs. 50%) and longer LOS (18 vs. 13 d) compared to quartiles II-IV. Impaired TNF release may be a manifestation of monocyte endotoxin tolerance and may be useful to diagnose sepsis.
目前，尚无可靠的诊断测试来识别脓毒症重症监护病房（ICU）患者。我们开展了多项研究，以验证以下假设：在脓毒症中，通过对脂多糖（LPS）刺激的肿瘤坏死因子（TNF）产生进行体外分析，可检测到体内内毒素暴露情况。我们从58名ICU患者和14名健康对照者中获取了肝素化全血（WB）。将样本在37℃下与±10 ng/mL的LPS孵育3小时。使用酶联免疫吸附测定法测量血浆TNF水平（平均值±平均标准误差）。回顾性获取临床数据，包括ICU住院时间（LOS）、呼吸机使用天数（VentD）、白细胞计数（WBC）和阳性培养结果（Clt+）。在ICU患者（4481±469）和对照者（6706±715）中观察到了广泛的LPS刺激的WB TNF产生范围（pg/mL）。根据绘制的LPS刺激的TNF值（pg/mL）分布，将患者分为四分位数（I-IV）。与四分位数II-IV（N = 44）相比，四分位数I中的患者（N = 14）TNF产生显著降低（<2000 pg/mL，P < 0.05），且需要更长的VentD时间（16天对10天，P < 0.05）。与四分位数II-IV相比，四分位数I中的患者感染发生率也更高（79%对50%），LOS更长（18天对13天）。TNF释放受损可能是单核细胞内毒素耐受的一种表现，可能有助于脓毒症的诊断。
