Involvement of tumor necrosis factor-alpha in the pathogenesis of activated macrophage-mediated hepatitis in mice.
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.
Nagakawa
J
J
Tsukuba Research Laboratories, Eisai Company Limited, Ibaraki, Japan.
Hishinuma
I
I
Hirota
K
K
Miyamoto
K
K
Yamanaka
T
T
Tsukidate
K
K
Katayama
K
K
Yamatsu
I
I
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*
D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D000410:Alanine Transaminase; D015064:16,16-Dimethylprostaglandin E2