Emndotoxin binding proteins and endotoxin-mediated macrophage reaction : Prospect for future treatment of liver cirrhosis

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1.In order to attain more physiological condition in the evaluation of macrophage function, we added 1% rat serum as a source of lipopolysaccharide (LPS) binding protein (LBP) and analyzed LPS-stimulated TNF-α production by various rat macrophages. TNF-α production of alveolar macrophages was much greater than Kupffer cells.2.Cytokine production of various macrophages was evaluated in rat with liver cirrhosis. TNF-α and IL1-β production by Kupffer cells was low and those by alveolar macrophages was high in cirrhotic rats compared with controls. Hepatocellular carcinoma grew more rapidly in cirrhotic liver, which may be partly related to depressed TNF-α and IL1-β production by Kupffer cells.3.Prostaglandin EP-4 agonist suppressed TNE-α production of rat -Kupffer cells and splenic macrophages. An addition of EP-4 agonist tended to antagonize the inhibitory effect of LPS on albumin synthesis of rat hepatocytes in the co-culture system.These results suggest that the modulation of macrophage function may become future therapeutic approach to liver cirrhosis.