IL-1 receptor antagonist anakinra downregulates inflammatory cytokines during renal normothermic machine perfusion: Preliminary results

IF 2.2 3区医学 Q3 ENGINEERING, BIOMEDICAL Artificial organs Pub Date : 2024-11-20 DOI:10.1111/aor.14909

Sarah A. Hosgood, Tom Moore, Alex Walker, Michael L. Nicholson

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Abstract

Background

The interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine kidneys.

Method

Paired porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice. Kidneys were then perfused with autologous whole blood using an ex vivo NMP platform. Kidneys were randomly allocated to receive anakinra or vehicle administered at the start of NMP. Cortical biopsies were collected at baseline before ischemic injury and at the end of NMP. Functional parameters were recorded and calculated, and inflammatory markers were measured by qPCR and ELISA techniques.

Results

During NMP, there were no statistically significant differences in renal blood flow, urine output, creatinine clearance or fractional excretion of sodium in the anakinra and control groups. The administration of anakinra significantly downregulated transcriptional expression of IL-6, Fas ligand and intercellular adhesion molecule 1 (p = 0.029, 0.029, 0.028, respectively).

Conclusion

Anakinra, an IL-1 receptor blocker, successfully attenuated the downstream inflammatory and immune-mediated response within the kidney during NMP.

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IL-1 受体拮抗剂 Anakinra 可在肾脏常温机器灌注过程中下调炎症细胞因子：初步结果。

背景：白细胞介素1（IL-1）细胞因子群在无菌性炎症中起着关键作用，可能是移植相关肾损伤的重要靶点。本研究探讨了在猪肾常温机器灌注（NMP）过程中使用非特异性 IL-1 受体拮抗剂 Anakinra 的效果：方法：配对的猪肾（n = 5 对）经过 15 分钟的温缺血和 2 小时的冰内静态冷藏。然后使用体外 NMP 平台为肾脏灌注自体全血。在 NMP 开始时，随机分配肾脏接受 anakinra 或给药。在缺血损伤前的基线和 NMP 结束时收集皮质活检组织。记录和计算功能参数，并通过 qPCR 和 ELISA 技术测量炎症标记物：结果：在 NMP 期间，肾血流量、尿量、肌酐清除率和钠的部分排泄量在 Anakinra 组和对照组之间没有明显的统计学差异。服用 Anakinra 可显著降低 IL-6、Fas 配体和细胞间粘附分子 1 的转录表达（p = 0.029、0.029、0.028）：结论：IL-1 受体阻断剂 Anakinra 成功地减轻了 NMP 期间肾脏内的下游炎症和免疫介导反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Artificial organs 工程技术-工程：生物医学

CiteScore

4.30

自引率

12.50%

发文量

303

审稿时长

4-8 weeks

期刊介绍： Artificial Organs is the official peer reviewed journal of The International Federation for Artificial Organs (Members of the Federation are: The American Society for Artificial Internal Organs, The European Society for Artificial Organs, and The Japanese Society for Artificial Organs), The International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, The International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation. Artificial Organs publishes original research articles dealing with developments in artificial organs applications and treatment modalities and their clinical applications worldwide. Membership in the Societies listed above is not a prerequisite for publication. Articles are published without charge to the author except for color figures and excess page charges as noted.