Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice.
The possible involvement of interleukin-1 alpha (IL-1 alpha) in the pathogenesis of murine hepatitis model induced with galactosamine and lipopolysaccharide (LPS) was investigated. The injection of 10 ng/mouse of LPS in combination with 10 mg/mouse of galactosamine into mice induced hepatic damage at 24 hours. Treatment with anti-mouse IL-1 alpha antiserum 30 min before galactosamine/LPS injection showed a tendency to reduce the liver injury, while pretreatment with anti-mouse tumor necrosis factor-alpha (TNF) antiserum significantly protected mice from liver injury. The use of recombinant murine TNF, instead of LPS, in combination with galactosamine could elicit hepatic damage, whereas recombinant murine IL-1 alpha could not substitute for LPS. However, recombinant murine IL-1 alpha enhanced the hepatotoxic effect of recombinant murine TNF in galactosamine-sensitized mice. These results suggest that TNF plays a major role in the pathogenesis of galactosamine/LPS hepatitis in mice and that IL-1 alpha acts synergistically with TNF in this hepatitis model.
Nagakawa
J
J
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Hishinuma
I
I
Hirota
K
K
Miyamoto
K
K
Yasuda
M
M
Yamanaka
T
T
Katayama
K
K
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D005688:Galactosamine / Q000633:toxicity*; D007106:Immune Sera / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007106:Immune Sera; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine