concanavalin-a and ubenimex

The effect of ubenimex on the release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from immuno-competent cells was studied. Ubenimex enhanced release of IL-1 from mouse peritoneal macrophages at 1.0 and 100 micrograms/ml in vitro and the release at 1.0 microgram/ml was larger. When ubenimex was administered to mice IL-1-releasing activity of the peritoneal macrophages was enhanced 3 and 5 days after the administration but not enhanced 1 day after the administration. Ubenimex also enhanced IL-2 release from rat spleen cells at 0.1 and 10 micrograms/ml, when concanavalin A (Con A) was added in the IL-2-releasing system. The enhancement was still observed with mouse spleen cells, when serum was further added. Moreover, thymocyte-proliferating activity was attained in the broths which rat spleen cells were incubated with ubenimex from 0.1 to 10 micrograms/ml in the absence and presence of Con A.

Topics: Animals; Concanavalin A; Humans; Interleukin-1; Interleukin-2; Leucine; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Rats; Rats, Inbred F344; Spleen

Few immunomodulators are available for the control of infectious disease. One reason has been the lack of a suitable protocol for evaluating such agents. We have presented a series of assays of immune function that will allow a standardized approach to this problem. The value of this protocol has been established using long-term low dose, and short-term high dose, administration of bestatin, a small molecular weight microbial product. The experiments were done using both normal and immunocompromised animals. Bestatin had no effect on circulating leukocytes or the reticuloendothelial system. Leukocyte mobilization and T cell responsiveness in immunocompromised animals were enhanced following bestatin treatment. The antibody response to SRBC doubled in normal animals while the same treatment schedule resulted in a marked reduction in the response to Escherichia coli lipopolysaccharide. These results have established the value of the protocol and identified some new immunomodulating properties of bestatin which may be useful in the control of infectious disease.

Topics: Adjuvants, Immunologic; Animals; B-Lymphocytes; Cell Movement; Concanavalin A; Cyclophosphamide; Drug Administration Schedule; Female; Hypersensitivity, Delayed; Immunity; Immunocompetence; Leucine; Male; Mice; Mice, Inbred Strains; Mononuclear Phagocyte System; T-Lymphocytes

Immunomodulatory and antitumor activities of the low molecular weight, microbially-derived immunomodulators, bestatin and forphenicinol are reviewed. In addition, the inhibitory effects of the antitumor antibiotics, aclacinomycin and oxanosine, on the generation of suppressor cells are also represented. It is suggested that these substances will be useful for cancer treatment by chemotherapy and/or immunotherapy.

Topics: Aclarubicin; Adjuvants, Immunologic; Animals; Antibiotics, Antineoplastic; Concanavalin A; Glycine; Leucine; Lymphocyte Activation; Mice; Molecular Weight; Naphthacenes; Neoplasms, Experimental; Ribonucleosides

Topics: Aminopeptidases; Animals; Cells, Cultured; Concanavalin A; Guinea Pigs; Kinetics; Leucine; Lipopolysaccharides; Lymphocyte Activation; Male; Pepstatins; Phytohemagglutinins; Protease Inhibitors