Eicosanoid profile and evidence for endotoxin tolerance in chronic ethanol-fed rats

The present study evaluated the role of endotoxin, prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and thromboxane B2 in alcoholic liver injury. Animals (4-5 per group per time period) were fed ethanol and either saturated fat (SE group) or corn oil (CE group) and sacrificed at various time intervals: 1, 2, and 4 weeks. Non parenchymal cells (NPC) were isolated and the spontaneous and LPS-stimulated production of eicosanoids was evaluated. In addition, severity of pathology, plasma levels of endotoxin, TXB2, LTB4 and PGE2 were compared in the two groups. The severity of fatty, liver, necrosis and inflammation was significantly greater in the CE group compared to the SE group after 1 month. Plasma endotoxin levels were significantly higher in the CE group vs. SE group at all time periods studied. PGE2 levels in NPCS and plasma were in general higher in the SE group. LTB4 levels in NPCS declined with time in the SE group; in contrast the levels rose in the CE group. There was no difference in LTB4 levels in plasma between the two groups. TXB2 levels in plasma and NPCS were significantly higher in the CE group at all times. The pattern of LPS-stimulated eicosanoid production by NPC in the two groups (SE and CE) suggested the development of endotoxin tolerance in the CE group. However, an additional modulatory effect of ethanol was also suggested by our findings.