Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK.
Int J Mol Sci. 2024 Jun 5;25(11):6231. doi: 10.3390/ijms25116231.
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1β, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.
肾缺血再灌注是导致急性肾损伤的常见原因，可导致显著的发病率和死亡率。目前临床实践中尚无有效的治疗方法。本荟萃分析旨在评估 IL-10 免疫疗法对肾缺血再灌注损伤的影响。检索了 Medline、Embase、Cochrane-library、Google Scholar 和 clinicaltrials.gov，检索时间截至 2023 年 3 月 31 日。纳入了研究 IL-10 免疫疗法治疗肾缺血再灌注的临床前和临床干预性研究。主要终点是缺血再灌注后肾功能（血清肌酐）。次要终点包括线粒体完整性、细胞增殖、调节性细胞死亡（TUNEL 检测）、炎症细胞因子表达（TNF-α、IL-6 和 IL-1β）、M1/M2 巨噬细胞极化、组织完整性（肾小管损伤评分）、长期肾纤维化（纤维化面积%）和不良事件（肺毒性、心脏毒性、肝毒性）。检索共返回 861 条记录。对这些记录进行筛选后，共纳入 16 篇全文，随后纳入 7 项动物研究，共涉及 268 只小鼠/大鼠。与对照组相比，IL-10 免疫疗法在给药后 24 小时内更有效地降低了血清肌酐（95%CI：-9.177，-5.601，I = 22.42%）。IL-10 免疫疗法促进了线粒体完整性和细胞增殖，减少了调节性细胞死亡（95%CI：-11.000，-4.184，I = 74.94%）。它降低了 TNF-α、IL-6 和 IL-1β的表达，导致局部巨噬细胞 M2 极化，降低了肾小管损伤评分（95%CI：-8.917，-5.755，I = 22.71%）和长期肾纤维化（95%CI：-6.963，-3.438，I = 0%）。未观察到不良结局。总之，IL-10 免疫疗法在肾缺血再灌注动物模型中安全地改善了结局；IL-10 免疫疗法的转化潜力需要在临床试验中进一步研究。
Zotero 插件
