General Intensive Care Unit, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Medical Intensive Care Unit, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
J Cell Mol Med. 2020 Jun;24(12):6622-6633. doi: 10.1111/jcmm.15309. Epub 2020 Apr 26.
The study of the human response to injury has been hampered by the inherent heterogeneity in the models and methods used. By studying a standard injury longitudinally, using individual patient-level analysis, we endeavoured to better describe its dynamics. We analysed clinical variables, clinical laboratory and plasma cytokines from 20 patients at five time points. Clustering analysis showed two prototype patterns of cytokine behaviour: a concordant type, where cytokines behave the same way for all patients (notably IL-0 and TNFα), and a variable type, where different patterns of expression are seen for different patients (notably IL-8, IL-6 and IL-1RA). Analysis of the cytokines at the individual patient-level showed a strong four-way correlation between IL-1RA, GCSF, MIP-1β and MCP-1. As it holds for most patients and not just on average, this suggests that they form a network which may play a central role in the response to gastro-intestinal injuries in humans. In conclusion, the longitudinal analysis of cytokines in a standard model allowed the identification of their underlying patterns of expression. We propose that the two prototype patterns shown may reflect the mechanism that separates the common and individual aspects of the injury response.
对人类对损伤的反应的研究受到所使用模型和方法固有异质性的阻碍。通过对标准损伤进行纵向研究，使用个体患者水平的分析，我们努力更好地描述其动力学。我们分析了 20 名患者在五个时间点的临床变量、临床实验室和血浆细胞因子。聚类分析显示细胞因子行为有两种典型模式：一种是一致性模式，即所有患者的细胞因子行为方式相同（特别是 IL-0 和 TNFα），另一种是可变模式，即不同患者的表达模式不同（特别是 IL-8、IL-6 和 IL-1RA）。对个体患者细胞因子的分析显示，IL-1RA、GCSF、MIP-1β 和 MCP-1 之间存在强烈的四向相关性。由于它适用于大多数患者而不仅仅是平均水平，这表明它们形成了一个网络，可能在人类胃肠道损伤反应中发挥核心作用。总之，在标准模型中对细胞因子进行纵向分析可以确定其潜在的表达模式。我们提出，所显示的两种典型模式可能反映了区分损伤反应的共同和个体方面的机制。
