Antiarthritic and immunoregulatory activity of 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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D005453:Fluorescence; D005857:Germanium / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009942:Organometallic Compounds; D051381:Rats; D011917:Rats, Inbred Lew; D013141:Spiro Compounds / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007376:Interleukin-2; D009942:Organometallic Compounds; D013141:Spiro Compounds; D005857:Germanium; D003208:Concanavalin A; C026818:spirogermanium; D006051:Aurothioglucose; D001310:Auranofin; D007213:Indomethacin