Algaba-Chueca Francisco, de-Madaria Enrique, Lozano-Ruiz Beatriz, Martínez-Cardona Claudia, Quesada-Vázquez Noé, Bachiller Victoria, Tarín Fabián, Such José, Francés Rubén, Zapater Pedro, González-Navajas José M
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain.
Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Gastroenterology, General Hospital of Alicante, Alicante, Spain.
Pancreatology. 2017 May-Jun;17(3):364-371. doi: 10.1016/j.pan.2017.03.006. Epub 2017 Mar 18.
Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification.
We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease.
Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis).
Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients.
急性胰腺炎是一种胰腺炎症性疾病，可导致显著的发病率和死亡率。炎症小体途径在许多炎症性疾病的发病机制中具有重要意义，但其在急性胰腺炎患者中的作用仍有待阐明。
我们进行了一项前瞻性研究，纳入了27例急性胰腺炎患者和16名健康对照者。我们分离了外周血单个核细胞（PBMCs），并评估了不同炎症小体的表达和激活情况及其与疾病临床进程的关联。
我们的结果显示，在疾病发作早期，急性胰腺炎患者的PBMCs中炎症小体复合物的几个成分表达升高，包括黑色素瘤2（AIM2）中缺失的炎症小体形成受体。与健康对照者的PBMCs相比，急性胰腺炎患者的PBMCs中AIM2或NLRP3炎症小体的激活导致IL-1β和IL-18的产生加剧。此外，这些患者中PBMCs的AIM2 mRNA表达和AIM2介导的IL-1β产生与全身炎症增加相关。最后，在发生短暂或持续性器官衰竭（中度或重度急性胰腺炎）的患者中，AIM2表达进一步增加。
我们的数据表明，AIM2炎症小体的表达和激活在急性胰腺炎病程早期增加，提示AIM2激活可能影响这些患者的全身炎症和器官衰竭。
