抗内毒素单克隆抗体对脓毒症大鼠TNF、IL-1、IL-6的影响

Effects of monoclonal antibody against endotoxin on TNF, IL 1 and IL 6 in the septic rats

脓毒症是全身炎症反应的临床表现，炎性细胞因子在炎症的反应过程中具有广泛的生理功能，是引起重症感染，感染性休克，多器官功能衰竭以至死亡的主要因素，维持机体应急状态下的自身稳定是治疗脓毒症的努力目标。针对革兰阴性菌感染所引起的脓毒症，寻找防止细菌的侵袭，提高机体免疫力的有效处理手段，我们首先制备并获得了Ｍ２Ｂ这株单克隆抗体，采用脓毒症大鼠预先给以Ｍ２Ｂ的方法，观察了Ｍ２Ｂ在脓毒症１６ｈ动物存活率和细胞因子的变化。本文结果表明预先给以Ｍ２Ｂ处理，动物在盲肠结扎穿孔１６ｈ存活率为９０％，而未预处理者存活率为３３％。手术前４ｈ，２ｈ动物分别接受从腹腔给预Ｍ２Ｂ１ｍｇ／ｋｇ预治疗，测定大鼠血中的３种细胞因子：肿瘤坏死因子（ＴＮＦ），白细胞介素１（ＩＬ－１），白细胞介素６（ＩＬ－６）。正常组，脓毒症组，治疗组分别为：（１）ＴＮＦ：（１９．１８±４．３３）细胞毒性％、（３９．９３±３．８４）和（２７．９２±６．８９）细胞毒性％。（２）ＩＬ－１：（２９．８０±３．２０）ｋＵ／Ｌ、（１４２．２５±２７．４６）和（６７．３３±２７．３５）ｋＵ／Ｌ。（３）ＩＬ－６：（８．３３±４．０８）ｋＵ／Ｌ、（２５．２７±６．４０）和（８．７?

The clinical manifestations of sepsis are the expressions of systemic inflammatory response mediated by endogenous mediators and cytokines secreated by the infected individual himself. Based on this understanding, various new approaches of anti inflammatory therapies for interrupting the inflammatory cascade have been investgigated. This study was designed to evaluate the effects of monoclonal antibody against endotoxin M2B on TNF, IL 1, and IL 6 in the septic rats. Sepsis were produced in rats by method of cecal ligation and perforation (CLP). Treatment animnals received M2B 2mg/kg prior to CLP. Results showed that serum TNF levels reduced from the sepsis group of 39.93±3.84 to 27.94±6.89%, (lysis P <0.01) in the treatment group, IL 1 from 142.25±27.46 to 67.33±27.35 kU/L( P <0.01); and IL 6 from 25.27±6.40 to 8.77±2.97 kU/L ( P <0.05). It is thus concluded that monclonal antibody M2B may be a useful agent in fighting sepsis if properly used in selected patients.