艾氯胺酮通过调节胸外科患者单核细胞的表型转化来减轻全身炎症

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-29 DOI:10.1016/j.lfs.2025.123594

Weiyun Shen , Yan Yan , Wenjuan Zhang , Junmei Xu , Zhijian Li , Lin Yang

{"title":"艾氯胺酮通过调节胸外科患者单核细胞的表型转化来减轻全身炎症","authors":"Weiyun Shen , Yan Yan , Wenjuan Zhang , Junmei Xu , Zhijian Li , Lin Yang","doi":"10.1016/j.lfs.2025.123594","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><div>To assess esketamine's anti-inflammatory effects during thoracic surgery and its modulation of immune responses.</div></div><div><h3>Material and methods</h3><div>In a randomized trial, 64 of 73 patients undergoing thoracic surgery were allocated into the Control (not receiving esketamine) or the ES-KTM group (intraoperative esketamine infusion). Blood routine tests were conducted one day before (T0) and one day after the surgery (T3). Plasma levels of tumor necrosis factor-α (TNF-α) and interleukine-10 (IL-10) were analyzed by ELISA, and cell surface markers including CD14, CD16, CD163, CD40, CX3CR1, CD206 were tested by cytometry at the entry to the surgical room (T1) and the skin closure (T2). For the in vitro study, esketamine at 10 μM was employed to treat the lipopolysaccharide (LPS) stimulated macrophage cell line-Raw264.7, and its effects were tested by cytometry and RNA sequencing analysis.</div></div><div><h3>Key findings</h3><div>Esketamine application reduces the count of neutrophils and monocytes, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic inflammatory index (SII), and enhances the lymphocyte counting and lymphocyte to monocyte ratio (LMR). Then, esketamine application decreases the plasma TNF-α levels, while maintaining the IL-10 level in comparison with the Control group. Additionally, esketamine reduced the proportion of intermediate monocytes, downregulates the expressions of CD16, CD40 and CX3CR1, while upregulates the CD206 expression. Finally, in the in-vitro study, esketamine inhibits the M1 pro-inflammatory markers in LPS-challenged macrophages, and downregulates multiple immune-related pathways.</div></div><div><h3>Significance</h3><div>Esketamine mitigates surgery-triggered inflammation by suppressing monocyte/macrophage proinflammatory activity and TNF-α release, offering dual anesthetic and immunomodulatory benefits.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123594"},"PeriodicalIF":5.2000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Esketamine mitigates systemic inflammation via modulating phenotypic transformation of monocytes in patients undergoing thoracic surgery\",\"authors\":\"Weiyun Shen , Yan Yan , Wenjuan Zhang , Junmei Xu , Zhijian Li , Lin Yang\",\"doi\":\"10.1016/j.lfs.2025.123594\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aim</h3><div>To assess esketamine's anti-inflammatory effects during thoracic surgery and its modulation of immune responses.</div></div><div><h3>Material and methods</h3><div>In a randomized trial, 64 of 73 patients undergoing thoracic surgery were allocated into the Control (not receiving esketamine) or the ES-KTM group (intraoperative esketamine infusion). Blood routine tests were conducted one day before (T0) and one day after the surgery (T3). Plasma levels of tumor necrosis factor-α (TNF-α) and interleukine-10 (IL-10) were analyzed by ELISA, and cell surface markers including CD14, CD16, CD163, CD40, CX3CR1, CD206 were tested by cytometry at the entry to the surgical room (T1) and the skin closure (T2). For the in vitro study, esketamine at 10 μM was employed to treat the lipopolysaccharide (LPS) stimulated macrophage cell line-Raw264.7, and its effects were tested by cytometry and RNA sequencing analysis.</div></div><div><h3>Key findings</h3><div>Esketamine application reduces the count of neutrophils and monocytes, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic inflammatory index (SII), and enhances the lymphocyte counting and lymphocyte to monocyte ratio (LMR). Then, esketamine application decreases the plasma TNF-α levels, while maintaining the IL-10 level in comparison with the Control group. Additionally, esketamine reduced the proportion of intermediate monocytes, downregulates the expressions of CD16, CD40 and CX3CR1, while upregulates the CD206 expression. Finally, in the in-vitro study, esketamine inhibits the M1 pro-inflammatory markers in LPS-challenged macrophages, and downregulates multiple immune-related pathways.</div></div><div><h3>Significance</h3><div>Esketamine mitigates surgery-triggered inflammation by suppressing monocyte/macrophage proinflammatory activity and TNF-α release, offering dual anesthetic and immunomodulatory benefits.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"371 \",\"pages\":\"Article 123594\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2025-03-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320525002280\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525002280","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

摘要

目的评价艾氯胺酮在胸外科手术中的抗炎作用及其对免疫反应的调节作用。材料与方法在一项随机试验中，73例接受胸外科手术的患者中有64例被分为对照组（未接受艾氯胺酮治疗）和ES-KTM组（术中输注艾氯胺酮）。术前1天（T0）、术后1天（T3）进行血常规检查。ELISA法检测患者血浆肿瘤坏死因子-α (TNF-α)、白细胞介素-10 （IL-10）水平，细胞计数法检测患者进入手术室（T1）和皮肤闭合（T2）时的细胞表面标志物CD14、CD16、CD163、CD40、CX3CR1、CD206。体外实验采用10 μM艾氯胺酮处理脂多糖（LPS）刺激的巨噬细胞raw264.7，并通过细胞术和RNA测序分析检测其作用。氯胺酮可降低中性粒细胞和单核细胞计数、中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）和全身炎症指数（SII），提高淋巴细胞计数和淋巴细胞与单核细胞比值（LMR）。与对照组相比，应用艾氯胺酮可降低血浆TNF-α水平，同时维持IL-10水平。此外，艾氯胺酮降低中间单核细胞比例，下调CD16、CD40和CX3CR1的表达，上调CD206的表达。最后，在体外研究中，艾氯胺酮抑制lps挑战巨噬细胞M1促炎标志物，下调多种免疫相关通路。艾氯胺酮通过抑制单核细胞/巨噬细胞促炎活性和TNF-α释放来减轻手术引发的炎症，提供双重麻醉和免疫调节益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Esketamine mitigates systemic inflammation via modulating phenotypic transformation of monocytes in patients undergoing thoracic surgery

Aim

To assess esketamine's anti-inflammatory effects during thoracic surgery and its modulation of immune responses.

Material and methods

In a randomized trial, 64 of 73 patients undergoing thoracic surgery were allocated into the Control (not receiving esketamine) or the ES-KTM group (intraoperative esketamine infusion). Blood routine tests were conducted one day before (T0) and one day after the surgery (T3). Plasma levels of tumor necrosis factor-α (TNF-α) and interleukine-10 (IL-10) were analyzed by ELISA, and cell surface markers including CD14, CD16, CD163, CD40, CX3CR1, CD206 were tested by cytometry at the entry to the surgical room (T1) and the skin closure (T2). For the in vitro study, esketamine at 10 μM was employed to treat the lipopolysaccharide (LPS) stimulated macrophage cell line-Raw264.7, and its effects were tested by cytometry and RNA sequencing analysis.

Key findings

Esketamine application reduces the count of neutrophils and monocytes, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic inflammatory index (SII), and enhances the lymphocyte counting and lymphocyte to monocyte ratio (LMR). Then, esketamine application decreases the plasma TNF-α levels, while maintaining the IL-10 level in comparison with the Control group. Additionally, esketamine reduced the proportion of intermediate monocytes, downregulates the expressions of CD16, CD40 and CX3CR1, while upregulates the CD206 expression. Finally, in the in-vitro study, esketamine inhibits the M1 pro-inflammatory markers in LPS-challenged macrophages, and downregulates multiple immune-related pathways.

Significance

Esketamine mitigates surgery-triggered inflammation by suppressing monocyte/macrophage proinflammatory activity and TNF-α release, offering dual anesthetic and immunomodulatory benefits.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.