Talukdar Rupjyoti
Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, 500 082, India.
India Alliance Wellcome DBT Labs, Institute of Translational Research, Hyderabad, India.
Indian J Gastroenterol. 2025 Jul 18. doi: 10.1007/s12664-025-01826-z.
Acute pancreatitis (AP) is a burgeoning challenge. The first week of the disease is generally considered early AP. Events that occur during this phase can determine the magnitude of subsequent events. Even after decades of research, there is still no curative therapy for early AP. One of the earliest events of clinical AP is the co-localization of zymogen and trypsinogen within autophagolysosome which is followed by trypsin activation. The resulting acinar injury releases damaged-associated molecular patterns (DAMPs) that trigger cytokine production by the resident immune cells. Concurrently, there will be neutrophil infiltration, endothelial dysfunction and capillary leak. The local intra-pancreatic inflammation will activate the circulating mononuclear cells traversing the inflamed pancreas and in turn, get activated and perpetuate the systemic inflammatory response syndrome (SIRS). This eventually triggers organ damage. Concurrently, another phenomenon called compensatory anti-inflammatory response syndrome (CARS) ensues, that makes the patient susceptible to infections including infected necrosis. CARS is characterized by the downregulation of human leukocyte antigen (HLA)-DR and results in immunosuppression. The intestine also has a substantial role in determining the severity progression of systemic events in AP. The three components of the intestine that have been implicated include gut mucosal barrier, the microbiota and intestinal lymph. Intestinal inflammation occurs as a part of SIRS and results in the loss of tight junctions and apoptosis of the intestinal epithelial cells thereby increasing the mucosal permeability. Meanwhile, there will be gut microbial dysbiosis resulting in the translocation of pathogens and pathogen-associated molecular patterns (PAMPS) into the circulation. This would result in infections, which was already facilitated by CARS. In addition, the intestinal lymph could also result in translocation of intestinal toxins to the systemic circulation thereby contributing to the severity of AP. This narrative review discusses the current understanding of the mechanisms of early AP and the clinical implications.
急性胰腺炎（AP）是一个日益严峻的挑战。疾病的第一周通常被认为是早期AP。在此阶段发生的事件可决定后续事件的严重程度。即使经过数十年的研究，早期AP仍没有治愈性疗法。临床AP最早的事件之一是酶原和胰蛋白酶原在自噬溶酶体内共定位，随后胰蛋白酶激活。由此产生的腺泡损伤释放出损伤相关分子模式（DAMPs），触发驻留免疫细胞产生细胞因子。同时，会有中性粒细胞浸润、内皮功能障碍和毛细血管渗漏。胰腺内局部炎症会激活穿过炎症胰腺的循环单核细胞，进而被激活并使全身炎症反应综合征（SIRS）持续存在。这最终会引发器官损伤。同时，另一种称为代偿性抗炎反应综合征（CARS）的现象随之出现，使患者易发生包括感染性坏死在内的感染。CARS的特征是人类白细胞抗原（HLA）-DR下调并导致免疫抑制。肠道在决定AP全身事件的严重程度进展方面也起着重要作用。与AP相关的肠道三个组成部分包括肠道黏膜屏障、微生物群和肠淋巴。肠道炎症作为SIRS的一部分发生，导致紧密连接丧失和肠上皮细胞凋亡，从而增加黏膜通透性。同时，会出现肠道微生物群失调，导致病原体和病原体相关分子模式（PAMPs）易位至循环中。这会导致感染，而CARS已经促成了感染的发生。此外，肠淋巴也可能导致肠道毒素易位至体循环，从而加重AP的严重程度。这篇叙述性综述讨论了目前对早期AP机制的理解及其临床意义。
