concanavalin-a and spirogermanium

Spirogermanium is a novel metal containing azaspirane compound with reported antitumor activity. The results of the present investigation demonstrate that spirogermanium also exhibits antiarthritic and immunoregulatory activities after p.o. administration to rats. Spirogermanium decreased hindleg inflammatory lesions of adjuvant arthritic rats when administered p.o. before or after the development of the arthritic lesions. After termination of spirogermanium administration, the adjuvant-injected hindleg lesions remained significantly suppressed for at least 2 weeks postdrug treatment; whereas, the uninjected, immune-mediated hindleg inflammation tended to increase postdrug treatment. In multiparameter ex vivo studies, untreated arthritic rats exhibited enhanced cyanine dye fluorescence in peripheral blood monocytes, enhanced interleukin (IL)-1 production by adherent spleen cells and depressed IL-2 and IL-3 production by splenic lymphocytes. Spirogermanium normalized these changes to various degrees, with the exception of the depressed IL-2 and IL-3 production. Spirogermanium administered to normal nonarthritic rats decreased mitogenic responses of spleen cells to Concanavalin A which was found to be caused, at least in part, by enhanced suppressor cell activity. The antiarthritic and immunoregulatory profile of spirogermanium appeared to be different from the profiles of the antiarthritic agents, auranofin and indomethacin.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Arthritis; Arthritis, Experimental; Auranofin; Aurothioglucose; Concanavalin A; Fluorescence; Germanium; Immunosuppressive Agents; Indomethacin; Interleukin-1; Interleukin-2; Macrophages; Male; Monocytes; Organometallic Compounds; Rats; Rats, Inbred Lew; Spiro Compounds; T-Lymphocytes, Regulatory

Daily oral administration of spirogermanium to Lewis rats resulted in the generation of radiation-resistant (2000 Rad) suppressor cells which inhibited the proliferative response of normal spleen cells to an optimum concentration of concanavalin A. These suppressor cells became evident after three to six days of spirogermanium administration. After one day's treatment, although no suppressor cells could be detected, the response of these cells to concanavalin A was less than 50% of controls. Experiments designed to characterize the cell type(s) responsible for this suppression resulted in the finding that T cell-'depleted' populations of spleen cells were more suppressive than T cell-'enriched' populations. The induction of suppressor cells by spirogermanium and the previously described activity in the adjuvant arthritic rat model suggest therapeutic potential for autoimmune diseases.

Topics: Animals; Antineoplastic Agents; Cells, Cultured; Concanavalin A; Germanium; Kinetics; Lymphocyte Depletion; Male; Organometallic Compounds; Rats; Rats, Inbred Lew; Spiro Compounds; Spleen; T-Lymphocytes, Regulatory