title: Pro- and anti-inflammatory response of acinar cells during acute pancreatitis. Effect of N-acetyl cysteine.
abstract: We investigate the ability of acinar cells to produce tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) at different stages of acute pancreatitis (AP). Since oxidative stress is involved in the inflammatory response, the effect of N-acetyl cysteine (NAC) has also been evaluated. AP was induced in rats by bile-pancreatic duct obstruction (BPDO). NAC (50 mg/kg) was administered 1h before and 1h after BPDO. Acinar cells were incubated for 4 h at 37 degrees C in 5% CO2 atmosphere in absence and presence of 24-h BPDO-PAAF (20%, v/v) as stimulant agent. Acinar production of TNF-alpha and IL-10 was analysed by flow cytometry. Plasma amylase activity and histological studies of the pancreas indicated the severity of AP. PAAF significantly stimulated the acinar production of TNF-alpha and IL-10 in control rats. TNF-alpha production was also significantly stimulated in acinar cells of rats with AP, although a decrease in the pro-inflammatory response was found from 6 h after BPDO onwards. However, acinar cells failed to produce IL-10 from 3 h after BPDO. The protective effect of NAC treatment against oxidative cell damage reduced the pancreatic injury and maintained and enhanced the ability of acinar cells to produce IL-10 at early AP stages. As long as acinar cells were not severely damaged in the course of AP, greater ability to produce cytokines in response to PAAF was found in those with higher forward scatter (R2 cells). We suggest that the capability of acinar cells to maintain an appropriate balance between the production of pro- and anti-inflammatory mediators could contribute to determine the degree of severity of AP.
authors.affiliation: Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ramudo
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Manso
authors.forename: Secundino
authors.initials: S
authors.lastname: Vicente
authors.forename: Isabel
authors.initials: I
authors.lastname: De Dios
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000208:Acute Disease; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D002478:Cells, Cultured; D005434:Flow Cytometry; D034321:Hyperamylasemia / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D010183:Pancreatic Ducts / Q000601:surgery; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000111:Acetylcysteine