Jorge D Machicado, Peter J Lee, Stacey Culp, Kimberly Stello, Phil A Hart, Mitchell Ramsey, Adam Lacy-Hulbert, Cate Speake, Zobeida Cruz-Monserrate, B Joseph Elmunzer, David C Whitcomb, Georgios I Papachristou
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Seven serum cytokines relevant to early acute pancreatitis pathogenesis, angiopoietin-2, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein-1, resistin, and soluble tumor necrosis factor-α receptor 1, were measured in sera collected 2 h pre- and post-ERCP. Levels were compared among healthy controls and ERCP participants who either did or did not develop PEP. Heat maps were constructed to perform a multidimensional exploratory analysis that aimed to determine the cytokine signatures associated with PEP and its participant-related risk factors (female sex, young age, and obesity).</p><p><strong>Results: </strong>A total of 65 participants were enrolled (36 undergoing ERCP and 29 healthy controls). Eight of the 36 (22.2%) ERCP participants developed PEP. Baseline IL-8 levels measured before ERCP were elevated in participants who developed PEP (7.5 vs. 14.8 pg/mL, P=0.02), and most strongly upregulated in women under 40 years of age. HGF levels post-ERCP were higher in participants with PEP (738.0 vs. 556.6 pg/mL, P=0.04), and most strongly upregulated in obese participants.</p><p><strong>Conclusions: </strong>Pre-ERCP IL-8 and post-ERCP HGF are associated with the development of PEP. Findings from this pilot study can inform the design of translational work in the immunopathogenesis of PEP.</p>","PeriodicalId":7978,"journal":{"name":"Annals of Gastroenterology","volume":"37 6","pages":"734-741"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574161/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cytokine signatures in post-endoscopic retrograde cholangiopancreatography pancreatitis: a pilot study.\",\"authors\":\"Jorge D Machicado, Peter J Lee, Stacey Culp, Kimberly Stello, Phil A Hart, Mitchell Ramsey, Adam Lacy-Hulbert, Cate Speake, Zobeida Cruz-Monserrate, B Joseph Elmunzer, David C Whitcomb, Georgios I Papachristou\",\"doi\":\"10.20524/aog.2024.0922\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Following endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) is the most common complication. The host's innate immune response to periprocedural pancreatic injury is the hallmark of its pathogenesis. Investigating cytokine signatures associated with PEP and its risk factors can guide understanding of PEP immunopathogenesis.</p><p><strong>Methods: </strong>We conducted a single-center, prospective, observational pilot study in adults at high-risk for PEP. Seven serum cytokines relevant to early acute pancreatitis pathogenesis, angiopoietin-2, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein-1, resistin, and soluble tumor necrosis factor-α receptor 1, were measured in sera collected 2 h pre- and post-ERCP. Levels were compared among healthy controls and ERCP participants who either did or did not develop PEP. Heat maps were constructed to perform a multidimensional exploratory analysis that aimed to determine the cytokine signatures associated with PEP and its participant-related risk factors (female sex, young age, and obesity).</p><p><strong>Results: </strong>A total of 65 participants were enrolled (36 undergoing ERCP and 29 healthy controls). Eight of the 36 (22.2%) ERCP participants developed PEP. Baseline IL-8 levels measured before ERCP were elevated in participants who developed PEP (7.5 vs. 14.8 pg/mL, P=0.02), and most strongly upregulated in women under 40 years of age. HGF levels post-ERCP were higher in participants with PEP (738.0 vs. 556.6 pg/mL, P=0.04), and most strongly upregulated in obese participants.</p><p><strong>Conclusions: </strong>Pre-ERCP IL-8 and post-ERCP HGF are associated with the development of PEP. 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引用次数: 0
摘要
背景:内镜逆行胰胆管造影术(ERCP)后胰腺炎(PEP)是最常见的并发症。宿主对围手术期胰腺损伤的先天性免疫反应是其发病机制的标志。研究与 PEP 及其风险因素相关的细胞因子特征可指导对 PEP 免疫发病机制的理解:我们在 PEP 高危成人中开展了一项单中心、前瞻性、观察性试点研究。在急性胰腺炎发作前和发作后 2 小时采集的血清中测量了与早期急性胰腺炎发病机制相关的七种血清细胞因子:血管生成素-2、肝细胞生长因子(HGF)、白细胞介素-6(IL-6)、IL-8、单核细胞趋化蛋白-1、抵抗素和可溶性肿瘤坏死因子-α受体 1。比较了健康对照组和ERCP参与者中发生或未发生PEP的血清水平。构建热图进行多维探索性分析,旨在确定与PEP及其参与者相关风险因素(女性、年轻和肥胖)有关的细胞因子特征:共有 65 名参与者(36 名接受 ERCP 检查者和 29 名健康对照者)参加了研究。在36名ERCP参与者中,有8人(22.2%)患上了PEP。ERCP术前测量的IL-8基线水平在发生PEP的参与者中升高(7.5 pg/mL对14.8 pg/mL,P=0.02),40岁以下女性的IL-8上调幅度最大。PEP患者在ERCP后的HGF水平较高(738.0 pg/mL vs. 556.6 pg/mL,P=0.04),肥胖患者的HGF上调幅度最大:结论:ERCP 前 IL-8 和ERCP 后 HGF 与 PEP 的发生有关。结论:ERCP 前 IL-8 和ERCP 后 HGF 与 PEP 的发生有关。这项试验性研究的结果可为 PEP 免疫发病机制转化工作的设计提供参考。
Cytokine signatures in post-endoscopic retrograde cholangiopancreatography pancreatitis: a pilot study.
Background: Following endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) is the most common complication. The host's innate immune response to periprocedural pancreatic injury is the hallmark of its pathogenesis. Investigating cytokine signatures associated with PEP and its risk factors can guide understanding of PEP immunopathogenesis.
Methods: We conducted a single-center, prospective, observational pilot study in adults at high-risk for PEP. Seven serum cytokines relevant to early acute pancreatitis pathogenesis, angiopoietin-2, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein-1, resistin, and soluble tumor necrosis factor-α receptor 1, were measured in sera collected 2 h pre- and post-ERCP. Levels were compared among healthy controls and ERCP participants who either did or did not develop PEP. Heat maps were constructed to perform a multidimensional exploratory analysis that aimed to determine the cytokine signatures associated with PEP and its participant-related risk factors (female sex, young age, and obesity).
Results: A total of 65 participants were enrolled (36 undergoing ERCP and 29 healthy controls). Eight of the 36 (22.2%) ERCP participants developed PEP. Baseline IL-8 levels measured before ERCP were elevated in participants who developed PEP (7.5 vs. 14.8 pg/mL, P=0.02), and most strongly upregulated in women under 40 years of age. HGF levels post-ERCP were higher in participants with PEP (738.0 vs. 556.6 pg/mL, P=0.04), and most strongly upregulated in obese participants.
Conclusions: Pre-ERCP IL-8 and post-ERCP HGF are associated with the development of PEP. Findings from this pilot study can inform the design of translational work in the immunopathogenesis of PEP.