Biliary pancreatitis-associated ascitic fluid activates the production of tumor necrosis factor-α in acinar cells*


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Abstract

Objective:Acute pancreatitis is associated with increased cytokine release from different cell sources. We have investigated the ability of acinar cells, in comparison with inflammatory peripheral blood cells, to produce tumor necrosis factor (TNF)-α in response to pancreatitis-associated ascitic fluid (PAAF).Design:Controlled, randomized animal study.Setting:University research laboratory.Subjects:Male Wistar rats.Interventions:Flow cytometry using phycoerythrin-labeled monoclonal anti-TNF-α antiserum.Measurements and Main Results:PAAF (20%, v:v) obtained from rats with acute pancreatitis induced by bile-pancreatic duct obstruction significantly increased TNF-α production in acinar cells, as measured by flow cytometry using phycoerythrin-labeled monoclonal anti-TNF-α antiserum. Neither heating of PAAF nor the addition of soybean trypsin inhibitor or neutralizing amounts of anti-TNF-α monoclonal antiserum reduced the acinar cell TNF-α production. Monocytes and lymphocytes did not produce TNF-α in response to PAAF. Likewise, the typical monocyte and lymphocyte stimulating factors—lipopolysaccharide (10 μg/μL) and phorbol 12-myristate 13-acetate (250 ng/mL) plus ionomycin (1 μg/mL), respectively—were not able to produce TNF-α in acinar cells. By comparison of the two acinar cell populations differentiated by flow cytometry, R2 cells (with higher forward scatter values) showed a greater ability to produce TNF-α in response to PAAF than R1 cells. Acinar cell nuclear factor-κB was activated, but TNF-α production was not totally inhibited in presence of N-acetyl cysteine (30, 100 mM).Conclusions:The production of TNF-α from different cell sources is selectively activated. PAAF may be involved in the pathophysiology of acute pancreatitis by TNF-α production in acinar cells through mechanisms partially mediated by nuclear factor-κB activation. PAAF components, such as TNF-α or trypsin, are not responsible for acinar cell activation. TNF-α was induced by heat-resistant PAAF factors, displaying acinar cells with higher forward scatter (R2) a greater ability to increase the TNF-α production than R1 cells.

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