Abstract
Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procured resected human pancreata to taurolithocolic acid (TLCS) and evaluated for acinar injury, cytokine release and interaction with peripheral blood mononuclear cells (PBMCs). We observed autophagy in acinar cells in response to TLCS exposure. There was also time-dependent release of IL-6, IL-8 and TNF-α from the injured acini that resulted in activation of PBMCs. We also observed that cytokines secreted by activated PBMCs resulted in acinar cell apoptosis and further cytokine release from them. Our data suggests that the earliest immune response in human AP originates within the acinar cell itself, which subsequently activates circulating PBMCs leading to SIRS. These findings need further detailed evaluation so that specific therapeutic targets to curb SIRS and resulting early adverse outcomes could be identified and tested.
Highlights
Clinical acute pancreatitis (AP) is a burgeoning challenge to clinicians and scientists
In order to confirm this, we further evaluated for the specific marker of autophagy, LC3, which was expressed 6-folds greater in the acinar cells from TLCS treated tissue fragments compared to controls (Fig. 4b and c)
Clinical AP is characterised by an early phase of systemic inflammatory response syndrome (SIRS) and organ dysfunction[2]
Summary
Clinical acute pancreatitis (AP) is a burgeoning challenge to clinicians and scientists. The initial phase that lasts for the first 1–2 weeks is characterised by systemic inflammatory response syndrome (SIRS) with or without multiorgan dysfunction, and is associated with the first peak of mortality. The second phase that is seen from the second week onwards is marked by infections (including infected pancreatic necrosis [IPN]) in susceptible patients, and sepsis associated multiorgan dysfunction. This results in the second peak of mortality. We used gallstone AP as a model since taurolithocolic acid (TLCS), a bile acid known to cause experimental AP in rodents[7,8], has been shown to cause injury to human pancreatic acinar cells via involvement of calcineurin and NF-κB9
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
