Alcohol exacerbates LPS-induced fibrosis in subclinical acute pancreatitis.

The role of pancreatic acinar cells in initiating fibrogenic responses during the early stages of alcoholic acute pancreatitis has not been evaluated. We investigated the ability of injured acinar cells to generate pancreatic fibrosis in acute pancreatitis. Rats were fed either an ethanol-containing or control diet over 14 weeks and euthanized 3 or 24 hours after a single lipopolysaccharide injection. Profibrotic transforming growth factor-β of acinar cells and pancreatic fibrosis were assessed by immunofluorescence, histological characteristics, and electron microscopy. Human pancreatic tissues were also evaluated. Periacinar cell fibrosis and collagen were exacerbated 24 hours after endotoxemia in alcohol-fed rats. Alcohol exposure exacerbated acinar cell-specific production of transforming growth factor β in response to lipopolysaccharide in vivo and in acinar cell-like AR42J cells in vitro. Although a morphological examination showed no visible signs of necrosis, early pancreatic fibrosis can be initiated by little or no pancreatic necrosis. Transforming growth factor β was also significantly increased in human acinar cells from patients with acute/recurrent pancreatitis compared with chronic pancreatitis tissue. Alcohol exacerbates lipopolysaccharide-induced pancreatic fibrosis during the early onset of mild, subclinical, acute pancreatitis. We suggest that multiple, subclinical, acute pancreatitis episodes can accumulate in fibrosis during the development of chronic pancreatitis, even if there is no history of acute pancreatitis.