THE PREVENTIVE EFFECTS OF OK432 ON ENDOTOXIN-INDUCED LIVER-INJURY - LIVER PROTECTION BY THE MODULATION OF HEPATIC MACROPHAGE FUNCTION

The present study was conducted to clarify whether endotoxin-induced l iver injury could be improved by modulating the function of hepatic ma crophages using OK432, an immunostimulant derived from Streptococcus. OK432 elevated the capacity of hepatic macrophages to produce superoxi de and tumor necrosis factor (TNF), and enhanced the mRNA expression o f interleukin-1-alpha, -beta, and TNF-alpha in liver nonparenchymal ce lls (NPC), However, intravenous (iv) preadministration of OK432 reduce d the mRNA expression of TNF-alpha in liver NPC enhanced by the endoto xin injection, decreased the serum level of GOT and lactic dehydrogena se (LDH), and improved the survival rate of endotoxin-injected rats. H istological examination revealed a significant reduction in cell vacuo lization and focal necrosis in the livers of the endotoxin-injected ra ts pretreated with OK432. These results indicate that hepatic macropha ges play a crucial role in endotoxin-induced liver injury, and that TN F-alpha is one of the factors most likely to be implicated in the deve lopment of endotoxin-induced liver injury. Thus, it is suggested that the administration of OK432 provides liver protection by modulating th e responsiveness of hepatic macrophages against endotoxin.