Kazue Kodama

Effect of Shi-Ka-Ron and Chinese Herbs on Cytokine Production of Macrophage in Immunocompromised Mice

Shi-Ka-Ron is a prescription composed of 8 crude extracts of Chinese herbs. It reduces suppression of cytokine production by peritoneal macrophages in mice Immunocompromised by the anti-tumor agent, cyclophosphamide (CY), in vivo. Although it dose not increase IL-1 production in vitro, it enhances TNF production. We found that Ginseng radix, Lithospermi radix, Astragli radix and Glycyrrhizae radix somewhat reduced suppression of cytokine production in CY treated macrophages. Especially, Glycyrrhizae radix shows an active immune response both in vivo and in vitro. Our results suggested that the mechanism underlying immunomodulation of Shi-Ka-Ron is closely related to cytokine production: each herb stimulating macrophages.

Immunopotentiating Activity of Whole Cells and Mini-Cells of Salmonella typhimurium

Salmonella typhimurium strain 9 produces mini‐cells during cell proliferation. Mini‐cells are viable but cannot proliferate since they do not contain chromosomal DNA. Effects of whole cells and mini‐cells of S. typhimurium on the immune responses were investigated, with the following results. Phagocytosis of peritoneal macrophages was enhanced by in vivo stimulation of both whole cells and mini‐cells. Cellular immunity against L1210 cells (mouse leukemia cells) and Sarcoma 180 cells was also enhanced by both whole cells and mini‐cells. Mini‐cells slightly stimulated in vitro blast cell transformation of normal mouse lymphocytes. Whole cells of S. typhimurium induced antibody‐forming cells to produce IgG of higher affinity but mini‐cells did not. Mini‐cells were not directly cytotoxic for normal lymphocytes or L1210 cells.

Synergistic anti-tumor effect of mini-cells prepared from Salmonella typhimurium with mitomycin C in EL4-bearing mice

SummaryA statistically significant increase in survival time was observed in EL4-bearing mice after a mini-cell inoculation. However, no case of survival for over 30 days was observed after an EL4 graft in mice treated with mini-cells alone. Fifty percent of the mice survived for 40 days after an EL4 transplantation when the mice were treated with both an IV injection of mini-cells and an SC injection of mitomycin C. The mini-cell injection restored the macrophage chemotaxis activity in EL4-bearing mice but did not restore the lymphocyte activities.

Purine Metabolic Enzymes in Lymphocytes: II. Adenosine Deaminase and Purine Nucleoside Phosphorylase Activities in the Immune Responses

ICR mice were immunized with sheep red blood cells (sRBC). Both adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in spleen lymphocytes increased faster than the serum antibody titer and reached a peak one week after the immunization. ADA activity increased significantly in T lymphocytes but not in B lymphocytes collected from the spleens of the immunized mice. A statistically significant increase in PNP activity was found in both T and B lymphocytes from the spleens of the immunized mice.

Cells participating in immunologic memory induced with RNA from the spleens of immunized mice.

Ribonucleic acid (immune RNA, iRNA) extracted from the spleens of mice immunized with heterologous red blood cells induced antigen‐specific immunologic memory. The type of cells (T cells, B cells) which participate in immunologic memory induced with iRNA was investigated. Immune RNA‐primed T cells cooperated with normal, iRNA‐primed or antigen‐primed B cells and induced a high IgM response. Immune RNA‐primed B cells did not cooperate with normal T cells, but did with iRNA‐ or antigen‐primed T cells. The activities of iRNA‐primed T and B cells were antigen‐specific.

Immunological Properties of TtT/M‐87 Cell Line Established from Murine Pituitary Tumor‐Associated Macrophages

TtT/M‐87 cell is a macrophage cell line established from thyrotropic pituitary tumor tissues in mouse. In this paper, we report the immunological properties of M‐87 cells as a model of tumor‐associated macrophage. Contrasting with resident peritoneal macrophages, M‐87 cells constitutively secreted small but significant amounts of TNF‐α and IL‐1α, which were detectable in both biological assays (cytotoxic activity for L929 and co‐mitogenic activity for Con A‐induced T cell proliferation, respectively) and ELISA, and produced larger amounts of these cytokines upon stimulation with LPS. They expressed MHC class II molecules on their cell surface without stimulation by IFN‐γ. The accessory or antigen‐presenting cell activity in antibody‐producing response of spleen lymphocytes to sheep red blood cells was shown to be much higher in M‐87 cells than normal peritoneal macrophages. In addition, when normal spleen lymphocytes were cultured with allogeneic tumor cells, such as EL‐4 and S‐180, in the presence of M‐87 cells, lymphocytes reactive to stimulator cells were activated to manifest inhibitory effect on the tumor cell growth and also to manifest specific cytotoxic effect on the allogeneic tumor cells. These results show that M‐87 cells derived from tumor‐associated tissue are activated macrophages and that they are inhibitory to tumor cell growth and augmentative in the induction of T‐cell‐mediated immune responses.

Immunological Characteristics of the Effector Cells Induced by a Combination Therapy with Cyclophosphamide and Allogeneic Lymphocytes

A significant inhibition of tumor growth was observed when sarcoma 180 (S180)-bearing ICR strain mice were treated by a combination therapy, with a low dose of cyclophosphamide (CY) and an inoculation of allogeneic lymphocytes collected from C57BL/6 mice. The growth-inhibitory effect was significantly increased by an inoculation of a relatively lower dose of allogeneic lymphocytes (1 x 10(5) cells) and CY. The effector cells induced in the mice treated with CY and allogeneic lymphocytes expressed the Lyt 1.2, Lyt 2.2, IL-2R antigens on their membrane surface and did not express the H2KbDb (donor H-2) antigen, and they showed a specific cytostatic activity against S180 cells. These results strongly suggested that a combination therapy with a low dose of CY with an inoculation of allogeneic lymphocytes augmented an induction of specific cytotoxic T lymphocytes in the tumor-bearing recipient mice.

Spontaneously Induced Suppressor Cells In Vitro: Nonspecific Suppression of In Vitro Antibody Formation

Nonspecific suppressor cells were induced during in vitro culture of normal mouse spleen cells (SPC) using the Marbrook culture system. The suppressor cells inhibited both the primary and secondary antibody‐formation responses antigen nonspecifically in vitro, and both IgM‐ and IgG‐responses were inhibited. The supernatants from suppressive precultured cells were not suppressive. The suppressor cells also inhibited the response of allogeneic SPC beyond H‐2 compatibility. The induction of the suppressor cells did not require the presence of antigen but required fetal calf serum (FCS) or both FCS and 2‐mercaptoethanol (2‐ME). The suppressor cells were generated from the nylon‐wool adherent, radiation‐sensitive T cell population. On the other hand, the suppressor cells were nylon‐wool nonadherent, relatively radiation‐sensitive T cells.