Chen Hanwen, Wang Yanhong, Zippi Maddalena, Fiorino Sirio, Hong Wandong
Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
School of the Second Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Front Immunol. 2025 Aug 20;16:1608618. doi: 10.3389/fimmu.2025.1608618. eCollection 2025.
Acute pancreatitis (AP) is a gastrointestinal disease characterized by inflammation of the pancreas and is associated with high rates of morbidity and mortality. The pathogenesis of AP involves a complex interplay of cellular and molecular mechanisms, including oxidative stress, damage-associated molecular patterns (DAMPs), and the infiltration of various immune cells. This review aims to provide a comprehensive overview of the molecular mechanisms underlying AP, the role of different immune cells in its progression and potential therapeutic perspectives. Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and the antioxidant defense system, plays a crucial role in AP. ROS not only contribute to cell necrosis and apoptosis, but also activate immune cells and perpetuate inflammation. DAMPs released from damaged cells activate the innate immune response by interacting with pattern recognition receptors (PRRs), leading to the recruitment of immune cells such as neutrophils, macrophages and dendritic cells. These immune cells further amplify the inflammatory response by releasing cytokines and chemokines. Neutrophils are among the first responders in AP, contributing to both tissue damage and repair, as well as the double-site sword effect of neutrophil extracellular traps (NETs). Other immune cells, including T cells, dendritic cells, mast cells and monocytes/macrophages, are involved in modulating the inflammatory response and tissue repair processes. The balance between pro- and anti-inflammatory immune responses is critical in determining the severity and outcome of AP. A table of targeted drugs or substances available in clinical trials is provided at the end of this paper, with the aim of providing available opportunities for clinical treatment. Nevertheless, precise targeted drugs are still urgently needed in clinical treatment, where more in-depth research is needed.
急性胰腺炎（AP）是一种以胰腺炎症为特征的胃肠道疾病，与高发病率和死亡率相关。AP的发病机制涉及细胞和分子机制的复杂相互作用，包括氧化应激、损伤相关分子模式（DAMPs）以及各种免疫细胞的浸润。本综述旨在全面概述AP潜在的分子机制、不同免疫细胞在其进展中的作用以及潜在的治疗前景。氧化应激以活性氧（ROS）与抗氧化防御系统之间的失衡为特征，在AP中起关键作用。ROS不仅导致细胞坏死和凋亡，还激活免疫细胞并使炎症持续存在。受损细胞释放的DAMPs通过与模式识别受体（PRRs）相互作用激活先天免疫反应，导致中性粒细胞、巨噬细胞和树突状细胞等免疫细胞的募集。这些免疫细胞通过释放细胞因子和趋化因子进一步放大炎症反应。中性粒细胞是AP中的首批反应细胞之一，对组织损伤和修复以及中性粒细胞胞外陷阱（NETs）的双刃剑效应都有贡献。其他免疫细胞，包括T细胞、树突状细胞、肥大细胞和单核细胞/巨噬细胞，参与调节炎症反应和组织修复过程。促炎和抗炎免疫反应之间的平衡对于确定AP的严重程度和结局至关重要。本文末尾提供了临床试验中可用的靶向药物或物质列表，旨在为临床治疗提供可用机会。然而，临床治疗中仍迫切需要精确的靶向药物，这需要更深入的研究。
