TNF but Not IL-1 Decreases Pancreatic Acinar Cell Survival without Affecting Exocrine Function: A Study in the Perfused Human Pancreas

Abstract

Substantial quantities of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are produced within the pancreatic parenchyma during acute pancreatitis. Recent evidence suggests that IL-1β and TNF-α propagate acute pancreatitis and intensify the resulting pancreatic acinar cell death. This study examines the direct effect of IL-1β and TNF-α on pancreatic acinar cells. Human pancreata (n= 6), harvested during organ procurement, were perfusedex vivothrough the splenic artery using a sterile, oxygenated colloid solution. Each pancreas was perfused with either recombinant human IL-1β or TNF-α for 2 h and subsequently with the cholecystokinin analogue caerulein (positive control). Venous effluent was collected continuously and amylase and lipase were determined at 15-min intervals. Pancreatic histology was graded at baseline and following cytokine and caerulein perfusion. To examine the long-term effects of these cytokines on acinar cell viability, additionalin vitrostudies utilized the AR42J acinar cell line which was exposed to either IL-1β or TNF-α with survival determined daily by MTT assay. Perfusion of the human pancreas with either IL-1β or TNF-α did not alter amylase, lipase, or histology. Caerulein did induce pancreatitis as measured by increased amylase, lipase, and pancreatic histology. Survival of pancreatic acinar cells decreased when they were incubated with TNF-α but not IL-1β. Although present in large amounts within the pancreas during acute pancreatitis, IL-1β and TNF-α have no direct effect on acinar cell viability or exocrine function acutely nor do they induce pancreatitis. When present for more than 24 h, however, TNF-α but not IL-1β has a dramatic effect on acinar cell survival.