Sterile inflammatory response in acute pancreatitis

Pancreas. 2012 Apr;41(3):353-7. doi: 10.1097/MPA.0b013e3182321500.


The initial injury in acute pancreatitis is characteristically sterile and results in acinar cells necrosis. Intracellular contents released from damaged cells into the extracellular space serve as damage-associated molecular patterns (DAMPs) that trigger inflammation. There is increasing evidence that this sterile inflammatory response mediated through DAMPs released from necrotic acinar cells is a key determinant of further pancreatic injury, remote organ injury, and disease resolution in experimental models. A number of DAMPS, including high-mobility group box protein 1, DNA, adenosine triphosphate and heat shock protein 70, have been shown to have a role in experimental pancreatitis. Many of these DAMPs are also detectable in the human pancreatitis. Genetic deletion and pharmacologic antagonism demonstrate that specific DAMP receptors, including Toll-like receptor (TLR) 4, TLR9, and P2X7, are also required for inflammation in experimental acute pancreatitis. Downstream DAMP-sensing components include nod-like receptor protein 3, caspase 1, interleukin-1β (IL-1), IL-18, and IL-1 receptor, and also are required for full experimental pancreatitis. These DAMP-mediated pathways provide novel therapeutic targets using antagonists of TLRs and other receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Humans
  • Inflammation / etiology*
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / therapy
  • Inflammation Mediators / metabolism*
  • Pancreas / immunology*
  • Pancreas / pathology
  • Pancreatitis / complications*
  • Pancreatitis / genetics
  • Pancreatitis / immunology
  • Pancreatitis / pathology
  • Pancreatitis / therapy
  • Signal Transduction* / genetics


  • Inflammation Mediators