Mononuclear phagocyte system responsiveness in CCl4-induced liver cirrhosis

In rats with CCl4-induced liver cirrhosis, a twofold decrease of blood clearance rate and a fourfold reduction in number of Kupffer cells taking up colloidal carbon particles has been demonstrated. Zymosan stimulation does not lead to granuloma-like structures in the liver of CCl4-cirrhotic rats. In cirrhotic rats, unlike controls, the cathepsin D activity of liver tissue is very little increased by zymosan treatment and there is virtually no increase in collagenolytic activity. The increase in PGE content in cirrhotic rat liver after prodigiosan stimulation was 2.5 times less than in stimulated control animals. In cirrhotic rats, the IL-1 producing capacity of blood monocytes in vitro in response to lipopolysaccharide drops almost fivefold. The total count of bone marrow-derived myeloid colonies in cirrhotic zymosan-stimulated animals was reduced by 1.5-fold whereas in control animals zymosan induced a 1.8-fold increase in the number of myeloid colonies. The number, uptake and nitroblue tetrazolium-reducing capacities of lung, spleen, peritoneal and bone marrow macrophages in animals with liver cirrhosis were only slightly increased in response to zymosan as compared to control animals. The low response of extrahepatic macrophages to stimuli in cirrhotic animals is thought to be due to their premobilization during the development of cirrhosis.