Sepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironment. Conversely, uncontrolled turnover can contribute to tissue damage. Systemic Inflammation is implicated to play a role in the regulation of ECM turnover, but the relationship between the two is largely unclear. We performed an exploratory study in 10 healthy male volunteers who were intravenously challenged with 2 ng/kg lipopolysaccharide (LPS, derived from Escherichia coli) to induce systemic inflammation. Plasma samples were collected before (T0) and after (T 1 h, 3 h, 6 h and 24 h) the LPS challenge. Furthermore, plasma was collected from 43 patients with septic shock on day 1 of ICU admission. Circulating neo-epitopes of extracellular matrix turnover, including ECM degradation neo-epitopes of collagen type I (C1M), type III (C3M), type IV (C4Ma3), and type VI (C6M), elastin (ELP-3) and fibrin (X-FIB), as well as the ECM synthesis neo-epitopes of collagen type III (PRO-C3), collagen type IV (PRO-C4) and collagen type VI (PRO-C6) were measured by ELISA. Patient outcome data were obtained from electronic patient records. Twenty-four hours after LPS administration, all measured ECM turnover neo-epitopes, except ELP-3, were increased compared to baseline levels. In septic shock patients, concentrations of all measured ECM neo-epitopes were higher compared to healthy controls. In addition, concentrations of C6M, ELP-3 and X-FIB were higher in patients with septic shock who ultimately did not survive (N = 7) compared to those who recovered (N = 36). ECM turnover is induced in a model of systemic inflammation in healthy volunteers and was observed in patients with septic shock. Understanding interactions between systemic inflammation and ECM turnover may provide further insight into mechanisms underlying acute and persistent organ failure in sepsis.

中文翻译：

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新表位检测可识别全身炎症和脓毒症中的细胞外基质周转：一项探索性研究

脓毒症与高发病率和死亡率相关，主要是由于全身炎症引起的组织损伤，导致器官衰竭和恢复受损。调节细胞外基质（ECM）周转对于维持健康的组织稳态以及响应组织微环境中与疾病相关的变化至关重要。相反，不受控制的周转会导致组织损伤。全身炎症在 ECM 周转的调节中发挥作用，但两者之间的关系很大程度上尚不清楚。我们对 10 名健康男性志愿者进行了一项探索性研究，这些志愿者接受 2 ng/kg 脂多糖（LPS，源自大肠杆菌）静脉注射，以诱导全身炎症。在 LPS 攻击之前 (T0) 和之后 (T 1 小时、3 小时、6 小时和 24 小时)收集血浆样本。此外，我们还从 43 名感染性休克患者入住 ICU 的第一天采集了血浆。细胞外基质周转的循环新表位，包括 I 型 (C1M)、III 型 (C3M)、IV 型 (C4Ma3) 和 VI 型 (C6M) 胶原蛋白、弹性蛋白 (ELP-3) 和纤维蛋白的 ECM 降解新表位通过 ELISA 测量 (X-FIB) 以及 III 型胶原蛋白 (PRO-C3)、IV 型胶原蛋白 (PRO-C4) 和 VI 型胶原蛋白 (PRO-C6) 的 ECM 合成新表位。患者结果数据从电子患者记录中获得。 LPS 给药后 24 小时，除 ELP-3 外，所有测得的 ECM 更新新表位均较基线水平有所增加。在感染性休克患者中，所有测量的 ECM 新表位的浓度均高于健康对照。此外，与康复者 (N = 36) 相比，最终未能存活的感染性休克患者 (N = 7) 的 C6M、ELP-3 和 X-FIB 浓度更高。 ECM 更新是在健康志愿者的全身炎症模型中诱导的，并在感染性休克患者中观察到。了解全身炎症和 ECM 更新之间的相互作用可能有助于进一步了解脓毒症急性和持续性器官衰竭的机制。