MOLECULAR MECHANISM OF INFLAMMATORY AND IMMUNOLOGICAL FACTORS INVOLVED IN DRUG-INDUCED LIVER INJURY

我们研究了炎症和免疫介质在四氯化碳诱导的肝损伤模型中的作用。四氯化碳皮下或腹腔给药分别在8小时和4小时后诱导血浆中白细胞介素-6 （IL-6）达到峰值，而腹腔给药则没有。四氯化碳给药后24 ~ 48小时，大鼠肝酶活性显著升高，但p.o.给药比s.c.和I.p.给药增加的速率要高。随着载体（玉米油）与四氯化碳比例的增加，IL-6的诱导作用减弱，肝酶的泄漏增加。地塞米松预处理可通过s.c.或I.p.途径明显抑制四氯化碳处理大鼠IL-6的诱导，并增加酶的泄漏。这些结果表明，IL-6诱导与肝损伤之间存在密切的负相关关系，提示四氯化碳后早期诱导的IL-6可能在肝损伤的发生发展中起抑制作用。

We have investigated the role of inflammatory and immune mediators in the carbon tetrachloride induced liver injury models. An administration of carbon tetrachloride through the subcutaneous (s.c.) or intraperitoneal (I.p.) route induced interleukln-6 (IL-6) in plasma with a peak at 8 and 4 hr later, respectively, but that through the per os (p.s.) route did not. The maker hepatic enzyme activities were increased with a peak 24 hr to 48 hr after carbon tetrachloride administration, however, the rate of increase was higher through the p.o. route than through the s.c. or I.p. route. As ratios of the vehicle (corn oil) to carbon tetrachloride were increased, the IL-6 induction was decreased and the leak of hepatic enzymes was augmented. Pretreatment with dexamethasone markedly suppressed the IL-6 induction and enhanced the enzyme leaks in the rats treated with carbon tetrachloride through the s.c. or I.p. route.These results represent the close reverse correlation between IL-6 induction and liver injury, suggesting the IL-6 induced in the early phase after carbon tetrachloride might play a suppressive role in the development of the liver injury.