The therapeutic effects of tumor necrosis factor monoclonal antibody and nitric oxide inhibitor on endotoxemia in splenectomized mice

Objective:The present study was performed to investigate the treatment effects of tumor necrosis factor （TNF） monoclonal antibody and nitric oxide inhibitor on endotoxemia in splenectomized mice.Methods:Mice were subjected to splenectomy followed by endotoxin challenge. Results:When 5 mg/kg endotoxin （E.coli O₁₁₁ B₄ LPS） was given intravenously, we found that the mortality rate of splenectomized mice was significantly higher than that of non-splenectomized mice （P＜0.01）. When the former group received anti-TNF monoclonal antibody （3 mg/kg）, the mortality rate was significantly decreased. Similarly, in splenectomized mice received 2 mg/kg L-NMMA （an nitric oxide synthase inhibitor）, the mortality rate was also decreased （P＜0.05）. However, in mice received 5 mg/kg L-NMMA, the mortality rate was dramatically increased.Conclusion:It is suggested that treatment with anti-TNF antibody and suitable dose of NO synthase inhibitor may play an important role in preventing overwhelming postsplenectomy infection.