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

Although the pathophysiology of acute pancreatitis appears to be greatly in fluenced 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 ra t model of severe acute pancreatitis on the ability of peritoneal macrophag es to produce tumor necrosis factor-alpha (TNF-alpha). In addition, we comp ared the responses of PAAF-treated and PAAF-untreated macrophages to lipopo lysaccharide (LPS) by evaluating their TNF-alpha production and nuclear fac tor-kappa B (NF-kappa B) activation. Incubation of peritoneal macrophages w ith the PAAF led to the rapid and prolonged activation of NF-kappa B and to TNF-alpha production. Pyrrolidine dithiocarbamate, a potent inhibitor of N F-kappa B activation, attenuated the macrophage TNF-alpha production by PAA F. Macrophages produced TNF-alpha in response to LPS, but the cytokine prod uction was significantly reduced when macrophages were pretreated with PAAF . The suppression of TNF-alpha production by PAAF pretreatment accompanied the impairment of NF-kappa B activation in response to LPS. These results i ndicate that the PAAF of severe acute pancreatitis may play important roles in the pathologic course of this disease through its effects on macrophage function.