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Effect of Sho-Saiko-To on interferon production of human peripheral blood mononuclear cells
WS26-6
*6
EFFECT OF SHO-SAIKO-TO ON INTERFERON PRODUCTION OF HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS S. Kakumu. T~rd Department of Internal Medicine, Nagoya University, School of Medicine Sho-saiko-to (TJ-9) is a blended Kampo Medicine (Japanese Herbal Medicine). It has many pharmacolo~c effects including immunoactivating action. Immune inter~ron (IFN 7) inhibits replication of viruses and exerts immunomodulatory acti~ties. The present study was undertaken to determine whether TJ-9 can induce IFN 7 production of peripheral blood mononuclear cells (PBMC) ~om healthy individuals. PBMC ~om 7 healthy su~ects were cultured with T J-9 in the presence or absence of suboptimal dose (2 ~g/ml) of concanavalin A (Con. A) for 3 days at 37°C in a 5% CO2 incubator. After culture, IFN 7 activities in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA) using horseradish peroxidase-co~ugated anti-human recombinant IFN 7 antibody. Low but definite amounts of IFN 7 ranging ~om 12.1 ±5.6 (mean ±SD) U/ml to 35.4 ±11.3 U/ml were detected i n a dose-dependent manner in cultures in the presence of various concentrations of TJ-9 (50 - 500 ~g/ml). TJ-9 also dose-dependently enhanced IFN 7 production in Con A~timulated cultures. When 100 ~g/ml of TJ-9 were added to the cultures together with Con A. maximum amounts of IFN 7 (363 ±85 U/ml) were generated. This value was significantly higher (p < 0.01 ) than that of Con A alone culture (232 ±59 U/ml). These findings indicate that T J-9 has some immunomodulatory activities and may explain the therapeutic effect of TJ-9 on certain types of chronic liver disease.
W S 2 6 - 7 *7 OF SHO-SAIKO-TO ON T-CELL COLONY FORMATION IN PERIPHERAL BLOOD OF PATIENTS WITH DECREASED IMMUNOLOGICAL FUNCTION J. Matsuda Department of Medicine, Teikyo University, School of Medicine, Tokyo, Japan Sho-Saiko-To, a representative Kampo Medicine (Japanese Herbal Medicine), is effective against various acute or chronic febrile and inflammatory diseases. Although these effects are presumed to be attributed to antiallergic and antiinflammatory reactions to the drug, there have been few reports on the detailing the mechanism. Here we examined the effects of the culture supernatant of monocytes incubated with Sho-Saiko-To on lymphocyte functions employing T-cell colony formation, which shows the function of helper T-lymphocytes, as an indicator. The peripheral blood monocytes, drawn from HIV antibody-positive homosexual men (HS) and hemophilics (HP) were incubated with various concentrations of Sho-Saiko-To medium and its components, are washed for 24 hours, incubated in a new culture medium for another 24 hours, and centrifuged to obtain the supernatant (CM(+)). CM(+) was added to monocyte depleted and cultured with PHA for T cell colony formation test. In HS and HP the colony formation was enhanced by addition of autogenous or allogenic CM(+). CM(-) of HS and HP depressed the colony formation in healthy adults, but the depressed colony formation was recovered by addition of CM(+). The results suggests that the tested drug is a BRM which induces ILl from monocytes. We are now running trials to administering the drug to HIV-positive patients, to follow their clinical courses. EFFECTS
WS26-8
-8
THE PROTECTIVE EFFECTS OF GOMISIN A IN AN EXPERIMENTAL MASSIVE HEPATIC CELL NECROSIS MODEL Y. Mizoguchi*, Y. Sakagami*, S. Seki*, K. Kobayashi* and S. Morisawa** *Third Department of Internal Medicine and **Department of Biochemistry, Osaka City University Medical School, Osaka, Japan When a small amount of grsm-negative lipopolysaccharide is intravenously injected into mice administered with heat-killed Propionibacterium acnes 7 days before, massive hepatic cell necrosis is induced and most of the mice die within 24 hours. In this experimentally-induced massive hepatic cell necrosis model, the adherent cells accumulated into the liver including macrophages and Kupffer cells are primed by Propionibacterium aches and activated by lipopolysaccharide, producing the cytotoxic factor. However~ when GOMISIN A, a lignan component from Shizandra chinensis, was administered with lipopolysaccharide, the induction of such severe liver damage was blocked. GOMISIN A increased the survival rate of the mice to more than 80% and improved the histological changes of the liver. In order to find out how GOMISIN A suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied in vitro the effects of GOMISIN A on the activation of liver adherent cells from which the cytotoxic factor is released and on the protection of hepatocytes from the cytotoxic factor. As a result, GOMISIN A not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it directly affected the hepatocytes and protected them from the cytotoxic factor.
40
*6
EFFECT OF SHO-SAIKO-TO ON INTERFERON PRODUCTION OF HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS S. Kakumu. T~rd Department of Internal Medicine, Nagoya University, School of Medicine Sho-saiko-to (TJ-9) is a blended Kampo Medicine (Japanese Herbal Medicine). It has many pharmacolo~c effects including immunoactivating action. Immune inter~ron (IFN 7) inhibits replication of viruses and exerts immunomodulatory acti~ties. The present study was undertaken to determine whether TJ-9 can induce IFN 7 production of peripheral blood mononuclear cells (PBMC) ~om healthy individuals. PBMC ~om 7 healthy su~ects were cultured with T J-9 in the presence or absence of suboptimal dose (2 ~g/ml) of concanavalin A (Con. A) for 3 days at 37°C in a 5% CO2 incubator. After culture, IFN 7 activities in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA) using horseradish peroxidase-co~ugated anti-human recombinant IFN 7 antibody. Low but definite amounts of IFN 7 ranging ~om 12.1 ±5.6 (mean ±SD) U/ml to 35.4 ±11.3 U/ml were detected i n a dose-dependent manner in cultures in the presence of various concentrations of TJ-9 (50 - 500 ~g/ml). TJ-9 also dose-dependently enhanced IFN 7 production in Con A~timulated cultures. When 100 ~g/ml of TJ-9 were added to the cultures together with Con A. maximum amounts of IFN 7 (363 ±85 U/ml) were generated. This value was significantly higher (p < 0.01 ) than that of Con A alone culture (232 ±59 U/ml). These findings indicate that T J-9 has some immunomodulatory activities and may explain the therapeutic effect of TJ-9 on certain types of chronic liver disease.
W S 2 6 - 7 *7 OF SHO-SAIKO-TO ON T-CELL COLONY FORMATION IN PERIPHERAL BLOOD OF PATIENTS WITH DECREASED IMMUNOLOGICAL FUNCTION J. Matsuda Department of Medicine, Teikyo University, School of Medicine, Tokyo, Japan Sho-Saiko-To, a representative Kampo Medicine (Japanese Herbal Medicine), is effective against various acute or chronic febrile and inflammatory diseases. Although these effects are presumed to be attributed to antiallergic and antiinflammatory reactions to the drug, there have been few reports on the detailing the mechanism. Here we examined the effects of the culture supernatant of monocytes incubated with Sho-Saiko-To on lymphocyte functions employing T-cell colony formation, which shows the function of helper T-lymphocytes, as an indicator. The peripheral blood monocytes, drawn from HIV antibody-positive homosexual men (HS) and hemophilics (HP) were incubated with various concentrations of Sho-Saiko-To medium and its components, are washed for 24 hours, incubated in a new culture medium for another 24 hours, and centrifuged to obtain the supernatant (CM(+)). CM(+) was added to monocyte depleted and cultured with PHA for T cell colony formation test. In HS and HP the colony formation was enhanced by addition of autogenous or allogenic CM(+). CM(-) of HS and HP depressed the colony formation in healthy adults, but the depressed colony formation was recovered by addition of CM(+). The results suggests that the tested drug is a BRM which induces ILl from monocytes. We are now running trials to administering the drug to HIV-positive patients, to follow their clinical courses. EFFECTS
WS26-8
-8
THE PROTECTIVE EFFECTS OF GOMISIN A IN AN EXPERIMENTAL MASSIVE HEPATIC CELL NECROSIS MODEL Y. Mizoguchi*, Y. Sakagami*, S. Seki*, K. Kobayashi* and S. Morisawa** *Third Department of Internal Medicine and **Department of Biochemistry, Osaka City University Medical School, Osaka, Japan When a small amount of grsm-negative lipopolysaccharide is intravenously injected into mice administered with heat-killed Propionibacterium acnes 7 days before, massive hepatic cell necrosis is induced and most of the mice die within 24 hours. In this experimentally-induced massive hepatic cell necrosis model, the adherent cells accumulated into the liver including macrophages and Kupffer cells are primed by Propionibacterium aches and activated by lipopolysaccharide, producing the cytotoxic factor. However~ when GOMISIN A, a lignan component from Shizandra chinensis, was administered with lipopolysaccharide, the induction of such severe liver damage was blocked. GOMISIN A increased the survival rate of the mice to more than 80% and improved the histological changes of the liver. In order to find out how GOMISIN A suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied in vitro the effects of GOMISIN A on the activation of liver adherent cells from which the cytotoxic factor is released and on the protection of hepatocytes from the cytotoxic factor. As a result, GOMISIN A not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it directly affected the hepatocytes and protected them from the cytotoxic factor.
40