Involvement of tumor necrosis factor-alpha in the pathogenesis of activated macrophage-mediated hepatitis in mice.
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| Abstract |
The possible involvement of tumor necrosis factor-alpha in the pathogenesis of an experimentally induced hepatitis was investigated. Balb/c mice were primed with Propionibacterium acnes to induce the infiltration of mononuclear cells into the liver. Immunohistochemical study showed that most of the accumulated mononuclear cells at 7 days were Mac-2 positive, suggesting that they were activated macrophages. An injection of lipopolysaccharide resulted in massive hepatic necrosis and high mortality in the mice within 24 hours. Plasma tumor necrosis factor-alpha activity initially rose sharply and then declined over 3 hours. The increase in plasma aminotransferase activity correlated well with the elevation of plasma tumor necrosis factor-alpha activity. Pretreatment with dexamethasone or 16,16-dimethyl-prostaglandin E2 attenuated not only the elevation of plasma tumor necrosis factor-alpha activity but also the increase in plasma aminotransferase activity and improved the survival rate. Passive immunization against tumor necrosis factor-alpha showed protective effects. These findings suggest that tumor necrosis factor-alpha released from activated macrophages may play a crucial role in the pathogenesis of this murine hepatitis.
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| Authors | J Nagakawa, I Hishinuma, K Hirota, K Miyamoto, T Yamanaka, K Tsukidate, K Katayama, I Yamatsu |
| Journal | Gastroenterology (Gastroenterology) Vol. 99 Issue 3 Pg. 758-65 (Sep 1990) ISSN: 0016-5085 [Print] United States |
| PMID | 2379780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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