The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain.
Francisco
F
Algaba-Chueca
Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Gastroenterology, General Hospital of Alicante, Alicante, Spain.
Enrique
E
de-Madaria
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.
Beatriz
B
Lozano-Ruiz
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Department of Pharmacology, University Miguel Hernández, Alicante, Spain.
Claudia
C
Martínez-Cardona
Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Gastroenterology, General Hospital of Alicante, Alicante, Spain.
Noé
N
Quesada-Vázquez
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain.
Victoria
V
Bachiller
Hematology Service, General Hospital of Alicante, Alicante, Spain.
Fabián
F
Tarín
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
José
J
Such
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 Clinical Medicine, University Miguel Hernández, Alicante, Spain.
Rubén
R
Francés
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 Pharmacology, University Miguel Hernández, Alicante, Spain.
Pedro
P
Zapater
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. Electronic address: gonzalez_josnav@gva.es.
José M
JM
González-Navajas
D000208:Acute Disease; D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D058847:Inflammasomes; D007249:Inflammation / Q000473:pathology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D010195:Pancreatitis / Q000473:pathology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D012333:RNA, Messenger
Inflammasomes; Inflammatory mediators; Innate immunity; Pancreatitis