UCLA researchers in the Department of Medicine and Surgery have developed a novel therapeutic for the prevention of late inflammatory complications in severe acute pancreatitis patients.
Acute pancreatitis, or sudden inflammation of the pancreas, a disease generally caused by gallstones or alcohol abuse, is a common reason for hospitalization worldwide. In some cases, life-threatening complications of acute pancreatitis may occur, such as multi-organ failure. Although multi-organ failure is often fatal, current treatment is supportive, with no known specific interventions. Pancreatic inflammation allows endotoxin (lipopolysaccharide, LPS), originating from Gram-negative bacteria in the gut lumen, to escape into the portal vein that drains the gut, activating inflammatory pathways in the liver and also producing systemic inflammation that damages other organs. Widespread inflammation increases gut permeability and further increases LPS uptake into circulation. In acute pancreatitis patients and also those with burns, trauma, and other acute insults, prevention of LPS release from the gut lumen into the portal vein could therefore decrease inflammation, and lessen the severity of late disease complications.
UCLA researchers have demonstrated that glucagon-like peptide 2 (GLP-2) acutely inhibits LPS uptake from the gut lumen into the portal vein. Administration of the GLP-2 analog in an acute pancreatitis model decreased pulmonary and hepatic inflammation while decreasing LPS entry into the portal vein. This treatment may decrease circulating LPS in severe acute pancreatitis patients and other patients with multi-organ failure following an acute insult, and could therefore reduce morbidity and mortality in critical illness.
This treatment has been successfully tested in mouse models of acute pancreatitis.
pancreatitis, acute pancreatitis, multi-organ failure, glucagon-like peptide-2, lipopolysaccharide, teduglutide, endotoxin, inflammation