Pancreatic colonization of fungi in the development of severe acute pancreatitis

Abstract

Acute pancreatitis is a common emergent disorder, a significant population of which develops the life-threatening condition, called severe acute pancreatitis (SAP). It is generally accepted that bacterial infection is associated with the development and persistence of SAP. In addition to bacterial infection, recent clinical studies disclosed a high incidence of fungal infection in patients with SAP. Moreover, SAP patients with fungal infection exhibit a higher mortality rate than those without infection. Although these clinical studies support pathogenic roles played by fungal infection in SAP, beneficial effects of prophylactic anti-fungal therapy on SAP have not been proved. Here we summarize recent clinical findings as to the relationship between fungal infection and the development of SAP. In addition, we discuss molecular mechanisms accounting for the development of SAP in the presence of fungal infection.

Keywords: acute pancreatitis; cytokines; fungi; intestinal barrier; walled-off necrosis.

Figure 1

Involvement of bacterial and fungal infection in the development of severe acute pancreatitis. Excessive drinking of alcohol induces auto-digestion of pancreatic tissues due to intrapancreatic activation of trypsinogen. Pro-inflammatory cytokine responses induced by initial inflammation dampen intestinal barrier function and allow entry of gut bacteria into the pancreas. Sensing of bacteria by nucleotide-binding oligomerization domain 1 (NOD1) and toll-like receptor 4 (TLR4) leads to a robust production of pro-inflammatory cytokines, which in turn increases intestinal permeability and translocation of gut bacteria. Intestinal barrier dysfunction also allows entry of gut fungi into the pancreas. Sensing of fungi by Dectin-1 may lead to a robust production of pro-inflammatory cytokines, which in turn increases intestinal permeability and translocation of gut fungi. Positive feedback loop between intestinal gut barrier dysfunction and pro-inflammatory cytokine responses induced by colonization of bacteria and/or fungi may be involved in the development of SAP displaying walled-off necrosis (WON). We created the Figure, which consisted of original cartoon pictures and CT pictures from patients who visited our hospital. CT pictures have not been published. This figure is original and based on our proposal and assumption.