Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Goethe-University, 60596 Frankfurt am Main, Germany.
Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, 89081 Ulm, Germany.
Int J Mol Sci. 2023 Jul 23;24(14):11830. doi: 10.3390/ijms241411830.
Trauma remains a leading cause of morbidity and mortality. Polytraumatized patients need a precise, early diagnosis to avoid complications such as multiorgan failure or sepsis. Inflammatory cytokines, commonly used for diagnosis, have a short half-life, which limits their efficacy as a diagnostic or prognostic marker. In this study, we hypothesized that cytokines in exosomes could have a longer half-life, and therefore could be used as diagnostic and prognostic markers in polytrauma patients. Plasma samples from polytraumatized patients (ISS ≥ 16, = 18) were collected in the emergency room (ER) 1, 2, 3 and 5 days after trauma. Plasma-exosomes were isolated via size exclusion chromatography from polytraumatized patients and healthy volunteers ( = 10). The systemic and exosomal concentrations of interleukin (IL)-6, IL-10, IL-1β and TNF were measured using high-sensitive ELISAs. To investigate the diagnostic and prognostic potential of exosomal cytokines, data were correlated with clinical outcome parameters (injury severity, ventilation time, time in ICU and survival) documented in the patients' electronic records. Despite the use of high-sensitive ELISAs, IL-1β and TNF alpha were not detected in exosomes. IL-6 and IL-10 were detectable in polytraumatized patient exosomes at all time points. A decrease over time of both systemic and exosomal IL-6 concentrations was observed. Furthermore, exosomal and systemic IL-6 concentrations moderately correlated (r = 0.63). Exosomal IL-6 in the ER moderately correlated with the Injury Severity Score (ISS) (mean 35.5 ± 11.5) (r = 0.45) and was associated with non-survival in polytrauma patients ( < 0.05). In contrast to IL-6, no correlation between systemic and exosomal IL-10 concentrations was found. Exosomal IL-10 concentrations remained unchanged throughout the observation time, whereas systemic IL-10 concentrations peaked in the ER and were significantly reduced after 24 h. Data from this study support our hypothesis that some cytokines (IL-10), but not all (IL-6), are detectable in exosomes significantly longer than they are in plasma. This might indicate that they are protected from degradation. Although we did not find a correlation between IL-10 exosomal concentration and patient outcome, our data confirm that exosomal cytokines are of interest as potential diagnostic and prognostic markers in polytrauma patients, and require further detailed research.
创伤仍然是发病率和死亡率的主要原因。多发伤患者需要进行精确、早期的诊断，以避免多器官衰竭或败血症等并发症。炎症细胞因子常用于诊断，但它们的半衰期较短，这限制了它们作为诊断或预后标志物的效果。在这项研究中，我们假设外泌体中的细胞因子半衰期可能更长，因此可以作为多发伤患者的诊断和预后标志物。在创伤后第 1、2、3 和 5 天，在急诊室（ER）采集多发伤患者（ISS≥16，n=18）的血浆样本。通过尺寸排阻色谱法从多发伤患者和健康志愿者（n=10）的血浆中分离外泌体。使用高灵敏度 ELISA 测量白细胞介素（IL）-6、IL-10、IL-1β和 TNF 的系统和外泌体浓度。为了研究外泌体细胞因子的诊断和预后潜力，将数据与患者电子病历中记录的临床结果参数（损伤严重程度、通气时间、入住 ICU 时间和存活率）相关联。尽管使用了高灵敏度 ELISA，但在外泌体中未检测到 IL-1β和 TNF alpha。在所有时间点均检测到多发伤患者外泌体中的 IL-6 和 IL-10。观察到系统和外泌体 IL-6 浓度随时间降低。此外，外泌体和系统 IL-6 浓度中度相关（r=0.63）。急诊室（ER）的外泌体 IL-6 与损伤严重程度评分（ISS）中度相关（平均 35.5±11.5）（r=0.45），与多发伤患者的非存活相关（<0.05）。与 IL-6 相反，系统和外泌体 IL-10 浓度之间没有相关性。外泌体 IL-10 浓度在整个观察期间保持不变，而系统 IL-10 浓度在 ER 中达到峰值，在 24 小时后显著降低。这项研究的数据支持我们的假设，即一些细胞因子（IL-10）而不是所有细胞因子（IL-6）在外泌体中的检测时间明显长于在血浆中的检测时间。这可能表明它们受到保护而免于降解。尽管我们没有发现 IL-10 外泌体浓度与患者结局之间的相关性，但我们的数据证实，外泌体细胞因子作为多发伤患者潜在的诊断和预后标志物具有重要意义，需要进一步详细研究。
