Acute pancreatitis affects non-parenchymal liver cells by a mechanism dependent on platelet-activating factor.

BACKGROUND/AIM: During acute experimental pancreatitis, inflammatory mediators/cytokines are released by the pancreas and enter the portal venous system, reaching the liver. We investigate some aspects of the liver cell function under conditions of acute pancreatitis and the effect of in vivo treatment with a selective platelet-activating factor (PAF) antagonist.

METHODS

Cells were isolated from Wistar rats 24 h after induction of acute pancreatitis by retrograde injection of sodium taurocholate into the main pancreatic duct. The non-parenchymal cell population was separated by Percoll gradient and the adherent cell population (Kupffer cells) obtained. The cells were cultured for 24 h and supernatants assayed for nitrite by Griess reaction and for tumour necrosis factor (TNF) by bioassay in L929 cells. The microbicidal activity was evaluated by killing of Candida albicans. The PAF antagonist WEB2170 (10 mg/kg i.v.) was administered 30 min before induction of pancreatitis.

RESULTS

We found that liver cells produce nitric oxide (NO) only under lipopolysaccharide stimulation and that WEB-2170 treatment reduces the NO production by liver cells in the pancreatitis group only. Cells from both groups produced TNF spontaneously, and the levels were further increased after lipopolysaccharide stimulation. WEB-2170 treatment did not affect the TNF levels. Moreover, killing of C. albicans by Kupffer cells wassignificantly increased by the PAF antagonist.

CONCLUSION

These results suggest that PAF released during acute pancreatitis upregulates the NO production by non-parenchymal liver cells and inhibits Kupffer cell microbicidal activity which could explain the increased bacterial dissemination observed in acute pancreatitis.