hepatitis C virus, making many patients uneasy. Under such ''Sho-saiko-to'' (TJ-9) consists of 7 herbal components.circumstances, interferon (IFN) was reported to be effective In Japan, it is widely prescribed to patients with chronic in chronic hepatitis C. 1-4 IFN became acceptable therapy for viral liver disease. TJ-9 is known to suppress liver canhepatitis C under the national insurance coverage in 1992; cer development and possess macrobiotic effects, but its the resulting expenses of this treatment have been substanmode of action is not fully understood. This study investial. In some patients, the hepatitis C virus was completely tigated the following: 1) cytokine production levels, eliminated from the body and hepatitis apparently cured. mainly interleukin (IL)-10, in peripheral blood mononuHowever, unfortunately, IFN was effective in only 30% to clear cells of chronic active hepatitis B and C patients, 40% of treated patients. IFN was ineffective in patients who and healthy volunteers; 2) effects of TJ-9 on these prohad high virus levels or advanced histological grades. In addiductions; and 3) effects of each of its herb components tion, some patients were withdrawn from treatment due to on cytokine production in cell fractions. Results showed side effects. For these ineffective cases in IFN therapies, and that without stimulants, IL-10 production in mononufor those who had poor tolerability to IFN, the most widely clear cells of hepatitis B and C patients was significantly prescribed oral medicines in Japan are the following: herbal lower than that of healthy subjects (P õ .01). IL-10 production induced by either phytohemagglutinin (PHA) or medicine ''Sho-saiko-to'' (TJ-9; Xiao-Chai-Hu-Tang in Chipokeweed mitogen (PWM) in mononuclear cells of hepa-nese) and ursodesoxycholic acid, and by intravenous injectitis C patients were significantly lower than in patients tion, strong neominophagen C. with hepatitis B (P õ .01) and healthy subjects (P õ .05).In Japan, many herbal medicines, which originated and IL-10 production induced by anti-CD3 or lipopolysaccha-have been used for several thousand years in China, are manride (LPS) was significantly lower than in healthy sub-ufactured with uniform quality and quantity of components jects (P õ .05). The addition of TJ-9 to the cultures as drugs for hospital uses. These medicines have received strongly induced IL-10, and this induction was mainly official approval, have been used by Japan's Western mediattributable to the effects of 2 components (scutellaria cine practitioners for 20 years, and their clinical efficacy has root and glycyrrhiza root) on the monocyte/macrophage been well recognized. Among them, TJ-9, which has been fraction. The production of IL-4 and IL-5 in cultures with used in treatment for pyretic diseases in China, is well known concanavalin A (conA) was significantly higher in pa-for gradually improving subjective symptoms and abnormal tients with hepatitis C than in the healthy subjects (P õ liver functions of patients with chronic viral live...

Inchinko-to (TJ-135) is a herbal medicine consisting of three kinds of crude drugs, and in Japan it is administered mainly to patients with cholestasis. The present study evaluated the effects of TJ-135 on concanavalin A (con A)-induced hepatitis in mice in vivo and con A-induced cytokine production in vitro. When mice were pretreated with oral TJ-135 for 1 week before intravenous con A injection, the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly decreased 8 h after con A administration (-82%, -96% and -66% respectively). In histological investigations, sub-massive hepatic necrosis accompanying inflammatory cell infiltration was not observed in mice pretreated with TJ-135. Serum levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and IL-2 were significantly lower in mice pretreated with TJ-135 compared with controls, while IL-10 levels were higher in these mice. Intrasplenic IL-12 levels were significantly lower in mice pretreated with TJ-135, while intrasplenic IL-10 levels were higher in these mice. In vitro, IL-10 production by splenocytes was increased by the addition of TJ-135 to the culture medium, whereas the production of IL-12 and IFN-gamma was inhibited. These results suggest that con A-induced hepatitis was ameliorated by pretreatment with TJ-135. With regard to the mechanism of these effects of TJ-135, we speculate that TJ-135 inhibits the production of inflammatory cytokine and enhances the production of anti-inflammatory cytokines. Therefore administration of TJ-135 may be useful in patients with severe acute hepatitis accompanying cholestasis or in those with autoimmune hepatitis.

Interleukin-12 (IL-12) is an important cytokine for maintainence of normal systemic defense and bioregulation. The Japanese herbal medicine Sho-saiko-to (TJ-9) has been administered to 1.5 million Japanese patients with chronic liver diseases. TJ-9 is known to significantly suppress cancer development in the liver and has macrobiotic effects. In the present study, we examined the in vitro production of IL-12 by circulating mononuclear cells from liver cirrhosis patients and the effects of TJ-9 on IL-12 production. The monocyte/macrophage fraction and the lymphocyte fraction of peripheral blood were obtained from 11 HCV-positive liver cirrhosis patients and 12 healthy subjects. Interleukin-12 levels in the supernatants were measured using ELISA kits. The levels of IL-12 produced by the patients fractions were significantly lower than those produced by healthy subjects (p < 0.01, p < 0.05). However, when TJ-9 was added to the cultures, the IL-12 production levels in both cell fractions increased approximately three fold, and the levels from the monocyte/macrophage fraction were almost the same as those from healthy subjects. This effect of TJ-9 was attributable to two of its seven herb components, that is, scutellaria root and glycyrrhiza root. One possible mechanism for the macrobiotic effects of TJ-9 on liver cirrhosis patients may be the improvement in IL-12 production.

'Sho-saiko-to' (TJ-9) is a Japanese herbal medicine that is commonly administered to patients with chronic viral liver disease in order to improve their overall physical condition and to prevent the development of liver cancer, The present in vitro study demonstrated that, by adding TJ-9 to cell cultures, there were dose-dependent increases in production levels of tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) in peripheral mononuclear cells of patients with hepatocellular carcinoma accompanied by liver cirrhosis. Increases in the production of TNF-alpha and G-CSF in control cell cultures exposed to different herbal medicines were low, and this indicates the specificity of the response increases in production of these cytokines to TJ-9. TNF-alpha and G-CSF are known to play important roles in the biological defence mechanism. Administration of TJ-9 may, therefore, be beneficial for patients afflicted with intractable liver diseases because it could mildly induce these cytokines.