title: Involvement of tumor necrosis factor-alpha in the pathogenesis of activated macrophage-mediated hepatitis in mice.
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.
authors.affiliation: Tsukuba Research Laboratories, Eisai Company Limited, Ibaraki, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nagakawa
authors.forename: I
authors.initials: I
authors.lastname: Hishinuma
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Yamanaka
authors.forename: K
authors.initials: K
authors.lastname: Tsukidate
authors.forename: K
authors.initials: K
authors.lastname: Katayama
authors.forename: I
authors.initials: I
authors.lastname: Yamatsu
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D006520:Hepatitis, Animal / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007116:Immunization, Passive; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D000410:Alanine Transaminase; D015064:16,16-Dimethylprostaglandin E2