Department of Neuroscience, Box 9303, West Virginia University, School of Medicine, Morgantown, WV, 26506-9303, USA; Department of Microbiology, Immunology, and Cell Biology, Box 9177, West Virginia University, School of Medicine, Morgantown, WV, 26506-9177, USA.
Department of Neuroscience, Box 9303, West Virginia University, School of Medicine, Morgantown, WV, 26506-9303, USA; Department of Microbiology, Immunology, and Cell Biology, Box 9177, West Virginia University, School of Medicine, Morgantown, WV, 26506-9177, USA.
Biochem Biophys Res Commun. 2024 Nov 26;735:150445. doi: 10.1016/j.bbrc.2024.150445. Epub 2024 Jul 24.
Sepsis, broadly described as a systemic infection, is one of the leading causes of death and long-term disability worldwide. There are limited therapeutic options available that either improve survival and/or improve the quality of life in survivors. Ilofotase alfa, also known as recombinant alkaline phosphatase (recAP), has been associated with reduced mortality in a subset of patients with sepsis-associated acute kidney injury. However, whether recAP exhibits any therapeutic benefits in other organ systems beyond the kidney is less clear. The objective of this study was to evaluate the effects of recAP on survival, behavior, and intestinal inflammation in a mouse model of sepsis, cecal ligation and puncture (CLP). Following CLP, either recAP or saline vehicle was administered via daily intraperitoneal injections to determine its treatment efficacy from early through late sepsis. We found that administration of recAP suppressed indices of inflammation in the gut and liver but did not improve survival or behavioral outcomes. These results demonstrate that recAP's therapeutic efficacy in the gut and liver may provide a valuable treatment to improve long-term outcomes in sepsis survivors.
败血症，广义上被描述为一种全身性感染，是全球范围内导致死亡和长期残疾的主要原因之一。目前可用的治疗方法有限，要么提高存活率，要么提高幸存者的生活质量。Ilofotase alfa（重组碱性磷酸酶）与败血症相关的急性肾损伤患者亚组的死亡率降低有关。然而，recAP 在肾脏以外的其他器官系统是否具有任何治疗益处尚不清楚。本研究的目的是评估 recAP 在败血症的小鼠模型——盲肠结扎和穿刺（CLP）中对存活率、行为和肠道炎症的影响。在 CLP 之后，通过每日腹腔内注射给予 recAP 或生理盐水载体，以确定其从早期到晚期败血症的治疗效果。我们发现，recAP 的给药抑制了肠道和肝脏的炎症指标，但没有提高存活率或行为结果。这些结果表明，recAP 在肠道和肝脏的治疗效果可能为改善败血症幸存者的长期预后提供了一种有价值的治疗方法。
