Introduction/Aims: Kupffer cells (KC) secrete potent mediators in response to bacterial products (LPS) and cytokines released during inflammatory events. This process might occur in severe acute pancreatitis (AP) leading to organ dysfunction and patient's death. The aims of this study were to investigate the NO and TNF production by KC in an “ex-vivo” model of AP and the participation of LPS, prostaglandin (PGE2) and PAF in this phenomenon.
Materials and Methods: Forty-nine rats were divided into four groups as follows: sham operation, AP, AP and intravenous anti-PAF antagonist (WEB-2170) injection, AP andintravenous anti-PGE2 (Indometacin) injection. AP was induced by injection of 2.5% sodium taurocholate into the commom biliopancreatic duct. KC were harvested from collagenase-digested livers and purified by adherence. Following overnight culture, 5 x 105 KC were repleted with fresh media with or without 10 mg/ml of LPS. Timed supernatants were collected at 6 and 48h to measure NO and TNF levels. NO and TNF data were analyzed by ANOVA. P<0,05 were considered significant. Results: The NO production by KC was significantly higher in AP group when compared to sham group in the presence of LPS (p<0,05). Treatment of AP group with anti-PAF antagonist or anti-PGE2 reduced NO levels significantly (p<0,05). There were no difference in the TNF production by KC in the presence or absence of LPS stimulation (p>0,05). Conclusions: In this model of AP the KC levels of NO but not TNF were increased after endotoxin stimulation. This effect was partially blocked by anti-PAF antagonist and by anti-PGE2. This suggest the existence of different pathways of LPS activity in the pathogenesis of this disease. Supported by FAPESP
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