K.G Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Pathology, Oslo University Hospital, Rikshospitalet, N-0027, Oslo, Norway.
Mol Med. 2021 Mar 26;27(1):29. doi: 10.1186/s10020-021-00288-1.
Alarmins are considered proximal mediators of the immune response after tissue injury. Understanding their biology could pave the way for development of new therapeutic targets and biomarkers in human disease, including multiple trauma. In this study we explored high-resolution concentration kinetics of the alarmin interleukin-33 (IL-33) early after human trauma.
Plasma samples were serially collected from 136 trauma patients immediately after hospital admission, 2, 4, 6, and 8 h thereafter, and every morning in the ICU. Levels of IL-33 and its decoy receptor sST2 were measured by immunoassays.
We observed a rapid and transient surge of IL-33 in a subset of critically injured patients. These patients had more widespread tissue injuries and a greater degree of early coagulopathy. IL-33 half-life (t) was 1.4 h (95% CI 1.2-1.6). sST2 displayed a distinctly different pattern with low initial levels but massive increase at later time points.
We describe for the first time early high-resolution IL-33 concentration kinetics in individual patients after trauma and correlate systemic IL-33 release to clinical data. These findings provide insight into a potentially important axis of danger signaling in humans.
警报素被认为是组织损伤后免疫反应的近端介质。了解它们的生物学特性可能为人类疾病(包括多发伤)中新的治疗靶点和生物标志物的开发铺平道路。在这项研究中,我们探讨了人类创伤后早期警报素白细胞介素-33(IL-33)的高分辨率浓度动力学。
创伤后立即、2、4、6 和 8 小时以及 ICU 中的每个早晨,连续采集 136 例创伤患者的血浆样本。通过免疫测定法测量 IL-33 及其诱饵受体 sST2 的水平。
我们观察到一组严重受伤的患者中 IL-33 迅速而短暂地激增。这些患者的组织损伤更广泛,早期凝血功能障碍程度更严重。IL-33 的半衰期(t)为 1.4 小时(95%置信区间 1.2-1.6)。sST2 表现出明显不同的模式,初始水平较低,但在稍后的时间点大量增加。
我们首次描述了创伤后个体患者早期高分辨率 IL-33 浓度动力学,并将全身 IL-33 释放与临床数据相关联。这些发现为人类危险信号的一个潜在重要轴提供了深入了解。