Critical Care Medicine Service, Hospital Clínico Universitario-SACYL/SEMICYUC, Avda Ramón y Cajal 3, 47005 Valladolid, Spain.
Cytokine. 2012 Mar;57(3):332-6. doi: 10.1016/j.cyto.2011.12.002. Epub 2011 Dec 23.
Identification of patients at increased risk of death is dramatically important in severe sepsis. Cytokines have been widely assessed as potential biomarkers in this disease, but none of the cytokines studied has evidenced a sufficient specificity or sensitivity to be routinely employed in clinical practice. In this pilot study, we profiled 17 immune mediators in the plasma of 29 consecutively recruited patients with severe sepsis or septic shock, during the first 24h following admission to the ICU, by using a Bio-Plex Human Cytokine 17-Plex Panel (Bio-Rad). Patients were 66.1year old in average. Twelve patients of our cohort died during hospitalization at the ICU, eight of them in the first 72h due to multiorganic dysfunction syndrom (MODS). Levels in plasma of three pro-inflammatory mediators (IL-6, IL-8, MCP-1) and of an immunosuppressive one (IL-10) were higher in those patients with fatal outcome. We developed a combined score with those cytokines showing to better predict mortality in our cohort based on the results of Cox regression analysis. This way, IL-6, IL-8 and IL-10 were included in the score. Patients were split into two groups based on the percentile 75 (P75) of the plasma levels of these three interleukins. Those patients showing at least one interleukin value higher than P75 were given the value "1". Those patients showing IL-6, IL-8, IL-10 levels below P75 were given the value "0". Hazard ratios for mortality at day 3 and day 28th obtained with the combined score were 2-3-fold higher than those obtained with the individual interleukins values. In conclusion, we have described a combined cytokine score associated with a worse outcome in patients with sepsis, which may represent a new avenue to be explored for guiding treatment decisions in this disease.
在严重脓毒症中,识别死亡风险增加的患者至关重要。细胞因子已被广泛评估为该疾病的潜在生物标志物,但研究中的任何一种细胞因子都没有表现出足够的特异性或敏感性,无法在临床实践中常规使用。在这项初步研究中,我们使用 Bio-Plex Human Cytokine 17-Plex 试剂盒(Bio-Rad)在 ICU 入院后 24 小时内,对 29 名连续招募的严重脓毒症或感染性休克患者的血浆中的 17 种免疫介质进行了分析。患者的平均年龄为 66.1 岁。我们队列中的 12 名患者在 ICU 住院期间死亡,其中 8 名患者在 72 小时内因多器官功能障碍综合征(MODS)死亡。在有致命结局的患者中,三种促炎介质(IL-6、IL-8、MCP-1)和一种免疫抑制介质(IL-10)的血浆水平更高。我们根据 Cox 回归分析的结果,使用那些在我们的队列中更好地预测死亡率的细胞因子开发了一个组合评分。通过这种方式,IL-6、IL-8 和 IL-10 被包含在评分中。根据这三种白细胞介素的血浆水平的第 75 百分位数(P75),患者被分为两组。那些至少有一种白细胞介素值高于 P75 的患者被给予值“1”。那些 IL-6、IL-8、IL-10 水平低于 P75 的患者被给予值“0”。用组合评分获得的第 3 天和第 28 天死亡率的危险比高于用单个白细胞介素值获得的危险比。总之,我们描述了一种与脓毒症患者不良结局相关的组合细胞因子评分,这可能为指导该疾病的治疗决策提供一个新的研究方向。