Experiment On IL-18 Antibody Counteracted Acute Immunity Hepatic Necrosis Induced By BCG+LPS In Mice

Mechanism of viral hepatitis is intimately correlation with disorder of immune system mediated by cytotoxicity of Thl cell. It is usually correlation with reaction chain induced by a series of cytokines, and IL-18 is the notablest one in series of cytokines which constituted cascade reaction chain. It may induce tissue apoptosis, inflammation, necrosis, and led to serious injury in liver, even to acute liver function failure and endanger the suffering life. By setting up hepatic necrosis model induced with BCG+LPS, we investigated the effect of IL-18 antibody to counteract action of IL-18, so as to block the reaction chain leading to hepatic apoptosis, inflammation, necrosis and kept hepatic tissue away from damage in earlier period. To study rudimentarily the role of IL-18 in acute immunity hepatic injury, and the important of blocking cascade reaction of cytokines by exerting IL-18 antibody in early stage.Based on the artificial Synthesis of mouse IL-18, experiment devide into two procedur: the first step, immunised mice used mixture of mouse IL-18 (10ug/time/each) added equal volume FCA or FIA, got the anti-IL-18 serum of mice according to immune procedure , detected the value of anti-IL-18 serum with ELISA: the concentration of the equal volum IL-18 50% Inhibited is 400pg/ml. The secondary step, in the experiment of counteracting acute immunity hepatic necrosis of mice induced by BCG+LPS. the models of acute immunity hepatic necrosis were induced by BCG 100 mg/kg via abdominal cavity injection and LPS 1 mg/kg was added after 10 days. Based on setting up BCG matched control, mice were divideinto two groups, anti-IL-18 antibody treatment group and model group, according to the different of disposal condition, exerting anti-IL-18 serum on mice (each 0.2ml) or not before the injection of LPS (lmg/kg) and then observed mice liver inflammation activity, detected serum IL-18 level and the expression level of IL-18 mRNA, TNF-alpha mRNA, IFN-gamma mRNA of the Liver tissue in each groups 24 hours later. The results displayed that mice's liver inflammation was notable, mass necrosis was observed in the model group and the count scores of inflammation activity was marked higher than the other two groups (P<0.01), so did the serum IL-18 level and the expression level of IL-18 mRNA, TNF- alpha mRNA, IFN-gamma mRNA of the Liver tissue(P<0.01). Correlation analysis suggested that inflammation activity was positive correlation with serum IL-18 level, the expression level of IL-18 mRNA, TNF-alpha mRNA and IFN-gamma mRNA of the Liver tissue. Their r value and p value have all significant differences in statistics.This experiment indicated that IL-18 played an important role in acute immunity hepatic injury before the cascade reaction of Thl cytokine which can accelerate markedly apoptosis and inflammation, and development of inflammation by self-positive feedback. By the neutralization of IL-18, IL-18 antibody can block the development of hepatic apoptosis, inflammation, necrosis and protect markedly the liver tissue from damage. It offered a new idea and method on treatment of acute and fulminate hepatitis.