Effect of tumor necrosis factor-α on acute liver necrosis of mice

Objective: To study the effect of tumor necrosis factor-α (TNF-α) on acute liver necrosis induced in mice. Methods: Male Balb/c mice received D-Galactosamine and lipopolysaccharide to induce acute liver necrosis. Serum levels of alanine transaminase (ALT) and TNFα were determined. The liver tissues were fixed for histopathologic analysis. The difference with pretreatment by using anti-TNF-α antibody was studied. Results: The mortality rate of mice with acute liver necrosis reached 60% 9 hours after injection. The serum levels of ALT began to increase from the 6th hour, and reached maximum at the 9th hour. The concentration of TNF-α reached a maximal value at the 2nd hour.The levels of TNF-α at every time point were significantly increased than that of control group (P0.01). The liver were induced with massive or submassive necrosis. But there were no death in mice with anti-TNF-antibody pretreatment. Serum levels of ALT were significantly reduced (P0.01). The histologic analysis showed only spotty necrosis or focal necrosis. Conclusion: The TNF-α is a key cytokine that induces liver necrosis. The treatment with anti-TNF-antibody prevents the liver necrosis.