Toshima Keiko, Mochida Satoshi, Arai Shin, Ishikawa Keiko, Matsui Atsushi, Fujiwara Kenji
Third Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
J Gastroenterol Hepatol. 1998 Sep;13(S1):S51-S54. doi: 10.1111/jgh.1998.13.s1.51.
Activated hepatic macrophages can provoke massive liver necrosis following endotoxin stimulation through microcirculatory disturbances due to sinusoidal fibrin deposition in rats pretreated with heat-killed Propionibacterium acnes. In these rats, FK506 (tachlorinus) administered 24 h before and at the time of endotoxin injection, significantly attenuated liver injury compared with the rats given no FK506. The effect of FK506 on hepatic macrophage activation and its action sites were studied in Propionibacterium acnes-treated rats. When rats received Propionibacterium acnes intravenously, hepatic-mRNA expression of interferon-γ-inducing factor and interleukin-2 and splenic-mRNA expression of interferon-γ were significantly increased compared with normal rats. Hepatic-mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, was also increased preceding the expressions of the three cytokines in the liver and spleen. FK506 administration attenuated hepatic-mRNA expression of interleukin-2 and both superoxide anions as well as tumour necrosis factor-α production by hepatic macrophages, but did not change CD14-mRNA expression in Propionibacterium acnes-treated rats. It is suggested that a cytokine network through interferon-γ-inducing factor, interferon-γ and interleukin-2 may operate during activation of hepatic macrophages in rats treated with heat-killed Propionibacterium acnes, while CD14 expression on the cells may increase independently of this network. FK506 seems to attenuate such activation by suppressing hepatic interleukin-2 expression, without affecting CD14 expression on the cells.
在经热灭活痤疮丙酸杆菌预处理的大鼠中，活化的肝巨噬细胞在内毒素刺激后可通过微循环紊乱引发大规模肝坏死，这是由于肝血窦纤维蛋白沉积所致。在这些大鼠中，在内毒素注射前24小时及注射时给予FK506（他克莫司），与未给予FK506的大鼠相比，肝损伤明显减轻。研究了FK506对痤疮丙酸杆菌处理的大鼠肝巨噬细胞活化及其作用位点的影响。当大鼠静脉注射痤疮丙酸杆菌时，与正常大鼠相比，肝内干扰素-γ诱导因子和白细胞介素-2的mRNA表达以及脾内干扰素-γ的mRNA表达显著增加。脂多糖及其结合蛋白复合物的受体CD14在肝和脾中的mRNA表达也在这三种细胞因子表达之前增加。给予FK506可减轻肝巨噬细胞白细胞介素-2的mRNA表达以及超氧阴离子和肿瘤坏死因子-α的产生，但不改变痤疮丙酸杆菌处理的大鼠中CD14的mRNA表达。提示在经热灭活痤疮丙酸杆菌处理的大鼠肝巨噬细胞活化过程中，可能存在通过干扰素-γ诱导因子、干扰素-γ和白细胞介素-2的细胞因子网络，而细胞上CD14的表达可能独立于该网络增加。FK506似乎通过抑制肝白细胞介素-2的表达来减轻这种活化，而不影响细胞上CD14的表达。
