Iron is an essential element for various physiological processes, but its levels must remain tightly regulated to avoid cellular damage. Similarly, iron plays a dual role in systemic inflammation, such as with sepsis. Leukocytes utilize iron to produce reactive oxygen species (ROS) to kill bacteria, but pathologically increased iron-catalyzed ROS production in sepsis can lead to damage of host cells, multi-organ failure and death. Temporary reduction in bioavailable iron represents a potential therapeutic target in sepsis. This study investigates the effect of the novel iron chelator, DIBI, in murine models of systemic (hyper-)inflammation: C57BL/6 mice were challenged with toxins from Gram-positive (Staphylococcus aureus: lipoteichoic acid, peptidoglycan) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae: lipopolysaccharide). Intravital microscopy (IVM) was performed to assess immune cell activation and its impact on microvascular blood flow in vivo in the microcirculation of the gut. Plasma inflammatory mediators were measured via multiplex assay, and morphologic change in intestinal tissue was evaluated. DIBI treatment decreased leukocyte (hyper-)activation induced by Gram-positive and Gram-negative toxins. In some cases, it preserved capillary perfusion, reduced plasma inflammatory markers and attenuated tissue damage. These findings support the utility of DIBI as a novel treatment for systemic inflammation, e.g., sepsis.

中文翻译：

---

革兰氏阳性和革兰氏阴性毒素诱导的全身炎症小鼠模型中的铁螯合。

铁是各种生理过程中必不可少的元素，但铁的含量必须严格控制以避免细胞损伤。同样，铁在全身性炎症（如败血症）中起着双重作用。白细胞利用铁产生活性氧（ROS）杀死细菌，但在脓毒症中病理上铁催化的ROS产生增加，可能导致宿主细胞受损，多器官衰竭和死亡。生物可利用铁的暂时减少代表败血症的潜在治疗靶标。这项研究调查了新型铁螯合剂DIBI在系统性（过度）炎症的小鼠模型中的作用：C57BL / 6小鼠受到革兰氏阳性（金黄色葡萄球菌：脂蛋白酸，肽聚糖）和革兰氏阴性细菌的毒素攻击（大肠杆菌和肺炎克雷伯菌：脂多糖）。进行体内显微镜检查（IVM）以评估免疫细胞的活化及其对肠道微循环体内微血管血流量的影响。通过多重测定测量血浆炎症介质，并评估肠组织的形态变化。DIBI治疗可减少革兰氏阳性和革兰氏阴性毒素诱导的白细胞（超）激活。在某些情况下，它可以保持毛细血管灌注，减少血浆炎症标记并减轻组织损伤。这些发现支持DIBI作为用于全身性炎症例如败血症的新疗法的用途。