Abstract
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 (5×104 units/mouse, i.v.)-injected mice was markedly lower at 4 h post-intoxication than that in the control, whereas the administration of rhTNF to Sho-saiko-to (500 mg/kg/d, p.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-2 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 (1 μg/ml) and rhTNF (1×104 units/ml) can effectively produce nitric oxide (NO), and ascertained the suppressive effect of Sho-saiko-to (500 mg/kg/d, p.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 (10-100 μl), 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 μg/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.
