Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University of Rostock, Rostock, Germany.
ARTCLINE GmbH, Rostock, Germany.
Artif Organs. 2023 Jul;47(7):1151-1162. doi: 10.1111/aor.14507. Epub 2023 Feb 14.
Immune cell dysfunction is a central part of immune paralysis in sepsis. Granulocyte concentrate (GC) transfusions can induce tissue damage via local effects of neutrophils. The hypothesis of an extracorporeal plasma treatment with granulocytes is to show beneficial effects with fewer side effects. Clinical trials with standard GC have supported this approach. This ex vivo study investigated the functional properties of purified granulocyte preparations during the extracorporeal plasma treatment.
Purified GC were stored for up to 3 days and compared with standard GC in an immune cell perfusion therapy model. The therapy consists of a plasma separation device and an extracorporeal circuit. Plasma is perfused through the tubing system with donor immune cells of the GC, and only the treated plasma is filtered for re-transfusion. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Efficacy of granulocytes regarding phagocytosis, oxidative burst as well as cell viability and metabolic parameters were assessed.
In pGC, the metabolic surrogate parameters of cell functionality showed comparable courses even after a storage period of 72 h. In particular, glucose and oxygen consumption were lower after extended storage. The course of lactate dehydrogenase concentration yields no indication of cell impairment in the extracorporeal circulation. The cells were viable throughout the entire study period and exhibited preserved phagocytosis and oxidative burst functionality.
The granulocytes demonstrated full functionality in the 6 h extracorporeal circuits after 3 days storage and in septic shock plasma. This is demonstrating the functionality of the system and encourages further clinical studies.
免疫细胞功能障碍是脓毒症免疫麻痹的核心部分。粒细胞浓缩物 (GC) 输注会通过中性粒细胞的局部作用引起组织损伤。通过体外血浆处理粒细胞的假设是展示更少副作用的有益效果。具有标准 GC 的临床试验支持这种方法。这项离体研究调查了在体外血浆处理过程中纯化粒细胞制剂的功能特性。
将纯化的 GC 储存长达 3 天，并在免疫细胞灌注治疗模型中与标准 GC 进行比较。该治疗包括血浆分离装置和体外回路。血浆通过带有 GC 供体免疫细胞的管系统进行灌注，仅处理后的血浆被过滤后再输血。供体免疫细胞在体外系统中保留并在治疗后丢弃。评估了粒细胞的吞噬作用、氧化爆发以及细胞活力和代谢参数的疗效。
在 pGC 中，即使在 72 小时的储存期后，细胞功能的代谢替代参数也显示出相似的过程。特别是，葡萄糖和氧气消耗在延长储存后降低。乳酸脱氢酶浓度的过程不能说明细胞在体外循环中的损伤。细胞在整个研究期间保持存活状态，并表现出保留的吞噬作用和氧化爆发功能。
在储存 3 天后的 6 小时体外回路中，以及在脓毒性休克血浆中，粒细胞表现出完整的功能。这证明了该系统的功能，并鼓励进一步的临床研究。
