Lipopolysacchardde induced production of pro-inflammatory cytokines and acute phase proteins in cultured pig hepatocytes; effects of pentoxifylline

摘要

Primary pig hepatocytes were used to study the effect of different doses of bacterial lipopolysaccharide (LPS) on hepalic acuie phase response. Proinflammatory cytokmes as welt as patterns of acute phase proteins were studied during a 72 hours incubation-time. Furthermore, the ability of pentoxifylline (PTX) to influence the LPS induced hepatic acute phase response was studied. Stimulation of pig hepatocytes with LPS resulted in a short and high peak of tumor necrosis factor-alpha (TNF-alpha) after2 hours. For mterleukin 6 (IL-6) a biphasic secretion profile was observed starting 4 hours after addition of LPS and reaching peak levels at 8 hours and 48 hours, respectively. No interleukin 1 (IL-1) levels could be measured as determined by D10 bioassay. Pig Major Acute Phase protein (pig MAP) proved to be the most sensitive acute phase protein. It was induced by LPS in a dose-dependent way. No significant elevation of C reactive protein (CRP) was measured. Synthesis of albumin by primary pig, hepatocytes was significantly decreased after stimulation with LPS. Pentoxifylline completely inhibited TNF-a production and decreased IL-6 levels from the second phase but not from the first phase. No significant effect of pentoxifylline on acute phase protein profiles was observed during 72 hours incubation time.