Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice

• Published in: Immunopharmacology and immunotoxicology Vol. 13; no. 4; p. 485
• Main Authors: Nagakawa, J, Hishinuma, I, Hirota, K, Miyamoto, K, Yasuda, M, Yamanaka, T, Katayama, K
• Format: Journal Article
• Language: English
• Published: England 1991
• Subjects: Animals; Chemical and Drug Induced Liver Injury - etiology; Galactosamine - toxicity; Immune Sera - immunology; Interleukin-1 - physiology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Recombinant Proteins - toxicity; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0892-3973
• DOI: 10.3109/08923979109019718

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.