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.
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 L 1210 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 L 1210 cells.
A 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.
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.
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