Ascitic fluid of experimental severe acute pancreatitis modulates the function of peritoneal macrophages

Although the pathophysiology of acute pancreatitis appears to be greatly influenced by the production of ascites, little is known about the mechanism. To investigate the effects of pancreatitis-associated ascitic fluid (PAAF) on macrophage function, we examined the effects of PAAF obtained from a rat model of severe acute pancreatitis on the ability of peritoneal macrophages to produce tumor necrosis factor-α (TNF-α. In addition, we compared the responses of PAAF-treated and PAAF-untreated macrophages to lipopolysaccharide (LPS) by evaluating their TNF-α production and nuclear factor-(K)B (NF(K)B) activation. Incubation of peritoneal macrophages with the PAAF led to the rapid and prolonged activation of NF-κB and to TNF-α production. Pyrrolidine dithiocarbamate, a potent inhibitor of NF-κB activation, attenuated the macrophage TNF-α production by PAAF. Macrophages produced TNF-α in response to LPS, but the cytokine production was significantly reduced when macrophages were pretreated with PAAF The suppression of TNF-α production by PAAF pretreatment accompanied the impairment of NF-κB activation in response to LPS. These results indicate that the PAAF of severe acute pancreatitis may play important roles in the pathologic course of this disease through its effects on macrophage function.