Goodman E R, Kleinstein E, Fusco A M, Quinlan D P, Lavery R, Livingston D H, Deitch E A, Hauser C J
Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA.
Arch Surg. 1998 Nov;133(11):1234-9. doi: 10.1001/archsurg.133.11.1234.
To evaluate the role of interleukin 8 (IL-8) in the regulation of neutrophil (PMN) apoptosis in normal plasma and plasma from patients with early, fulminant acute respiratory distress syndrome (ARDS).
Experimental study using cultured human PMNs.
University hospital, level I trauma center.
Plasma was obtained from 6 patients with early, fulminant posttraumatic ARDS (mean Injury Severity Score, 26). All samples were drawn within 24 hours after injury. Plasma was also taken from 13 healthy control subjects. These controls were also used as sources of PMNs.
Effect of early, fulminant ARDS and normal plasma on spontaneous apoptosis, CD16, and CD11-b expression in PMNs in vitro; levels of IL-8 in plasma; correlation of extracellular IL-8 concentration with rate of PMN apoptosis; and effect of IL-8 blockade on PMN apoptosis, CD16, and CD11-b expression in ARDS and normal plasma.
Plasma from patients with early, fulminant ARDS inhibited spontaneous PMN apoptosis at 24 hours (35%+/-5% vs 54%+/-5%; P=.01). Neither CD16 nor CD1l-b differed significantly between the 2 groups. The mean plasma level of IL-8 in patients with early, fulminant ARDS was 359+/-161 pg/mL vs 3.0+/-0.4 pg/mL in healthy controls (P<.05). Interleukin 8 inhibited apoptosis in plasma-free medium at low doses (1-50 pg/mL) but had no significant effect at higher doses (100-5000 pg/mL) (P<.05). Interleukin 8 blockade with monoclonal antibody suppressed apoptosis in normal plasma (28%+/-5% with monoclonal antibody vs 51%+/-5% without monoclonal antibody; P=.008) but not in plasma from patients with early, fulminant ARDS (29%+/-5% with monoclonal antibody vs 34%+/-6% without monoclonal antibody; P=.67). It had no effect on CD16 or CD11-b expression in either plasma.
Plasma from patients with early, fulminant ARDS contains soluble factors that inhibit PMN apoptosis in vitro. Low levels of IL-8 inhibit PMN apoptosis in normal plasma. Although plasma levels of IL-8 are markedly elevated in early, fulminant ARDS, IL-8 is not directly responsible for the antiapoptotic effect of plasma from patients with early, fulminant ARDS.
评估白细胞介素8（IL-8）在正常血浆以及早期暴发性急性呼吸窘迫综合征（ARDS）患者血浆中对中性粒细胞（PMN）凋亡的调节作用。
采用培养的人PMN进行的实验研究。
大学医院，一级创伤中心。
从6例早期暴发性创伤后ARDS患者（平均损伤严重度评分26）获取血浆。所有样本均在受伤后24小时内采集。还从13名健康对照者采集血浆。这些对照者也作为PMN的来源。
早期暴发性ARDS和正常血浆对体外PMN自发凋亡、CD16和CD11-b表达的影响；血浆中IL-8水平；细胞外IL-8浓度与PMN凋亡率的相关性；以及IL-8阻断对ARDS和正常血浆中PMN凋亡、CD16和CD11-b表达的影响。
早期暴发性ARDS患者的血浆在24小时时抑制PMN自发凋亡（35%±5%对54%±5%；P = 0.01）。两组之间CD16和CD11-b均无显著差异。早期暴发性ARDS患者的血浆IL-8平均水平为359±161 pg/mL，而健康对照者为3.0±0.4 pg/mL（P<0.05）。白细胞介素8在低剂量（1 - 50 pg/mL）时抑制无血浆培养基中的凋亡，但在高剂量（100 - 5000 pg/mL）时无显著作用（P<0.05）。用单克隆抗体阻断白细胞介素8可抑制正常血浆中的凋亡（单克隆抗体组为28%±5%，无单克隆抗体组为51%±5%；P = 0.008），但对早期暴发性ARDS患者血浆中的凋亡无抑制作用（单克隆抗体组为29%±5%，无单克隆抗体组为34%±6%；P = 0.67）。对两种血浆中的CD16或CD11-b表达均无影响。
早期暴发性ARDS患者的血浆含有在体外抑制PMN凋亡的可溶性因子。低水平的IL-8抑制正常血浆中的PMN凋亡。虽然早期暴发性ARDS患者血浆中IL-8水平显著升高，但IL-8并非早期暴发性ARDS患者血浆抗凋亡作用的直接原因。
