Pathophyisological analysis of endotoxemia and septisemia & effectiveness of suppression of liver macrophages.

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Our goal of this project is establishment of therpy for hepatic failure caused by endotoxemia and septisemia. So analysis of mechanisms of activation of liver macrophage have been done.In this study, we clarified that gadolinium chloride (GdC13) reduced mortality in rats injected with a lethal dose of endotoxin. However, plasma tumor necrosis factor (TNR) levels were not affected by GdC13 treatment. The mononuclear phagocyte system is situateed mainly in the liver and spleen. We suspected that the spleen macrophages probably compensate for dysfunction of liver macrophages and plasma TNF levels are affected by splenic macrophages. We investigated the function of splenic macrophages with respect to changes in plasma TNF,and carried out immunohistochemical study to investigate the repopulation of macrophges under the condition of dysfunction of liver macrophages with or without splenectomy. We got the results that large liver macrophages were eliminated after GdC13 injection and the splenic marcophages were not affected by GdC13 treatment. TNF levels were also not affected by the splenic macrophages and they do not compensate for dysfunction of liver macrophages after GdC13 treatment. In our future research about endotoxemia and septisemia, we should focus on an anlysis of mechanisms of activation of liver macrophages.