EFFECTS OF ANTITUMOR-ACTIVITY AND PROTECTION OF SHOCK SYMPTOMS BY A TRADITIONAL CHINESE MEDICINE (SHO-SAIKO-TO) IN RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR ADMINISTERED MICE

The effects of a traditional Chinese medicine Sho-saiko-to (Kampo pres cription) were investigated on the various metabolic disorders and ant itumor activity of recombinant human tumor necrosis (rhTNF) administer ed to mice. The glycogen level in liver of rhTNF (5 X 10(4) units/mous e, i.v.)-injected mice was markedly lower at 4 h post-intoxication tha n that in the control, whereas the administration of rhTNF to Sho-saik o-to (500 mg/kg/d, p.o.)-pretreated mice resulted in a greater level o f glycogen than that in rhTNF alone-treated mice. In mice pretreated w ith Sho-saiko-to, the level of fibrinogen 4 h after rhTNF injection ma rkedly increased as compared to that in mice treated with rhTNF alone. We also estimated the NO2- in murine macrophage cell line J774A.1 usi ng mice serum after administration of Sho-saiko-to. Our results clearl y demonstrated that J774A.1 cells stimulated with endotoxin (1 mu g/ml ) and rhTNF (1 X 10(4) units/ml) can effectively produce nitric oxide (NO), and ascertained the suppressive effect of Sho-saiko-to (500 mg/k g/d, p.o.)-pretreated serum on NO generation by endotoxin/TNF-activate d J774A.1 cells. When the cells were incubated with endotoxin/TNF and Sho-saiko-to pretreated serum (10-100 mu l), the NO level was signific antly lower than that in control serum incubated with endotoxin/TNF al one. The effect of Sho-saiko-to (1 and 10 mu g/ml) on in vitro cytotox icity by rhTNF in Meth-A Sarcoma cells was observed to be in a dose de pendent fashion. In addition, there was a remarkable enhancement of an titumor activity of rhTNF by Sho-saito-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 rhTN F-induced antitumor activity.