TNF BUT NOT IL-1 DECREASES PANCREATIC ACINAR CELL-SURVIVAL WITHOUT AFFECTING EXOCRINE FUNCTION - A STUDY IN THE PERFUSED HUMAN PANCREAS

Substantial quantities of interleukin-1 beta (IL-1 beta) and tumor nec rosis factor-alpha (TNF-alpha) are produced within the pancreatic pare nchyma during acute pancreatitis. Recent evidence suggests that IL-1 b eta and TNF-alpha propagate acute pancreatitis and intensify the resul ting pancreatic acinar cell death, This study examines the direct effe ct of IL-1 beta and TNF-alpha on pancreatic acinar cells. Human pancre ata (n = 6), harvested during organ procurement, were perfused ex vivo through the splenic artery using a sterile, oxygenated colloid soluti on. Each pancreas was perfused with either recombinant human IL-1 beta or TNF-alpha for 2 h and subsequently with the cholecystokinin analog ue caerulein (positive control). Venous effluent was collected continu ously and amylase and lipase were determined at 15-min intervals. Panc reatic histology was graded at baseline and following cytokine and cae rulein perfusion. To examine the longterm effects of these cytokines o n acinar cell viability, additional in vitro studies utilized the AR42 J acinar cell line which was exposed to either IL-1 beta or TNF-alpha with survival determined daily by MTT assay. Perfusion of the human pa ncreas with either IL-1 beta or TNF-alpha did not alter amylase, lipas e, or histology, Caerulein did induce pancreatitis as measured by incr eased amylase, lipase, and pancreatic histology, Survival of pancreati c acinar cells decreased when they were incubated with TNF-alpha but n ot IL-1 beta. Although present in large amounts within the pancreas du ring acute pancreatitis, IL-1 beta and TNF-alpha have no direct effect on acinar cell viability or exocrine function acutely nor do they ind uce pancreatitis. When present for more than 24 h, however, TNF-alpha but not IL-1 beta has a dramatic effect on acinar cell survival. (C) 1 998 Academic Press.