STUDIES ON AN EXPERIMENTALLY INDUCED ACUTE HEPATIC FAILURE IN MICE

Difference between Hepatotoxic Factor and Tumor Necrosis Factor

Abstract

When heat-killed Propionibacterium acnes (P. acnes) and a small amount of endotoxin lipopolysaccharide (LPS) were intravenously injected into mice at a week's interval, most animals were died of massive liver necrosis within 24 hours. Our previous studies suggested that adherent cells accumulated in liver and primed by P. acnes could produced cytotoxic factor(s) once activated by LPS.
Since tumor necrosis factor (TNF) is also produced from activated macrophages, we designed our experiment to clarify the difference between the cytotoxic factor and TNF. Some TNF activity was detected in mouse sera 2 hours after injecting of LPS in our experimental system. However, such TNF-contained sera did not exhibit any cytotoxicity for the isolated normal liver cells. In the culture supernatants containing a remarkable cytotoxic activity for liver cells, little TNF activity was detectable. The chelating agent, o-phenanthroline which is known to block TNF production did not exhibit any reduction in cytotoxic activity. Taking together with our previous physio-chemical observations of the cytotoxic factor(s), it is much likely that our cytotoxic factor may be different from TNF.