Abstract
The rapid production and release of a large number of inflammatory cytokines can cause excessive local and systemic inflammation in severe acute pancreatitis (SAP) and multiple organ dysfunction syndrome (MODS), especially pancreatitis-associated acute lung injury (P-ALI), which is the main cause of early death in patients with SAP. The NLRP3 inflammasome plays an important role in the maturation of IL-1β and the inflammatory cascade. Here, we established a model of SAP using wild-type (NLRP3+/+) and NLRP3 knockout (NLRP3−/−) mice by intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS). Pathological injury to the pancreas and lungs, the inflammatory response, and neutrophil infiltration were significantly mitigated in NLRP3−/− mice. Furthermore, INF-39, an NLRP3 inflammasome inhibitor, could reduce the severity of SAP and P-ALI in a dose-dependent manner. Our results suggested that SAP and P-ALI were alleviated by NLRP3 deficiency in mice, and thus, reducing NLRP3 expression may mitigate SAP-associated inflammation and P-ALI.
Highlights
Acute pancreatitis (AP) is an inflammatory disease that is usually diagnosed by acute abdominal pain and an increase in amylase and lipase concentrations in serum
The severity of severe acute pancreatitis (SAP) was significantly alleviated in NLRP3−/−
The levels of amylase in both serum and peritoneal lavage fluid (PLF) decreased in NLRP3−/− mice compared with those in NLRP3+/+ mice after the establishment of SAP (Figure 2)
Summary
Acute pancreatitis (AP) is an inflammatory disease that is usually diagnosed by acute abdominal pain and an increase in amylase and lipase concentrations in serum. More than 20% of patients with AP have severe acute pancreatitis (SAP). In contrast to mild AP, which has a mortality rate of less than 1%, the mortality rate for SAP is much higher: 10% with sterile and 25% with infected pancreatic necrosis [1]. SAP is frequently associated with acute lung injury and respiratory dysfunction. Several studies have provided some insights into the pathogenesis of acute respiratory insufficiency associated with AP. The limited knowledge of molecular mechanisms underlying the development of pancreatitisassociated acute lung injury (P-ALI) may explain the lack of specific clinical therapies [2]
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