Effects of Antitomor Activity and Protection of Shock Symptoms by a Traditional Chinese Medicine (Sho-Saiko-To) in Recombinant Human Tumor Necrosis Factor Administered Mice

摘要

The effects of a traditional Chinese medicine Sho-saiko-to (Kampo prescription) were investigated on the various metabolic disorders and antitumor activity of recombinant human tumor necrosis factor (rhTNF) administered to mice. The glycogen level in liver of rhTNF (5xlO4 units/mouse, i.v.)-injected mice was markedly lower at 4h post-intoxication than that in the control, whereas the administration of rhTNF to Sho-saiko-to (500mg/kg/d, />.o.)-pretreated mice resulted in a greater level of glycogen than that in rhTNF alone-treated mice. In mice pretreated with Sho-saiko-to, the level of fibrinogen 4 h after rhTNF injection markedly increased as compared to that in mice treated with rhTNF alone. We also estimated the NO^" in murine macrophage cell line J774A.1 using mice serum after administration of Sho-saiko-to. Our results clearly demonstrated that J774A.1 cells stimulated with endotoxin (Ifig/ml) and rhTNF (1 xlO4 units/ml) can effectively produce nitric oxide (NO), and ascertained the suppressive effect of Sho-saiko-to (500mg/kg/d,/?.o.)-pretreated serum on NO generation by endotoxin/TNF-activated J774A.1 cells. When the cells were incubated with endotoxin/TNF and Sho-saiko-to pretreated serum (10—lOO/il), the NO level was significantly lower than that in control serum incubated with endotoxin/TNF alone. The effect of Sho-saiko-to (1 and 10/ig/ml) on in vitro cytotoxicity by rhTNF in Meth-A Sarcoma cells was observed to be in a dose dependent fashion. In addition, there was a remarkable enhancement of antitumor activity of rhTNF by Sho-saiko-to pretreatment in mice. These findings suggest that the Kampo prescription Sho-saiko-to may protect mice from severe shock syndrome by rhTNF, and that it may enhance rhTNF-induced antitumor activity.