Immunomodulatory activity and non-specific suppressor cell generation by spirogermanium in murine and rat models of cell-mediated immunity.
Spirogermanium (SG) is a metal-containing compound reported to have antitumor, antiarthritic, antimalarial and immunoregulatory activity. In this study we have demonstrated that treatment of mice and rats with spirogermanium results in an inhibition of autoimmune disease and cell-mediated immune (CMI) responses. Prophylactic administration of SG inhibited the development of adjuvant-induced arthritis and the DTH response to purified protein derivative (PPD) in Lewis strain rats. SG treatment was also able to alleviate the symptoms of experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats. In two strains of mice, BDF1 and C57B1/6, the DTH response to sheep red blood cells could be suppressed by intraperitoneal (i.p.) administration of SG. The spleens of both mice and rats that have been treated with this drug contain suppressor cells which inhibit the response of normal cells to concanavalin A (Con A) and the mixed lymphocyte reaction. In addition, the generation of cytotoxic T cells (CTL) in the murine MLR is abrogated in the presence of these suppressor cells. The suppressor cells were radiation-resistant (2000 rad), indomethacin-insensitive and were not depleted by treatment with anti-Thy-1.2 antiserum plus complement. These results suggest that SG modulates cell-mediated immune responses in vivo by the induction of non-specific suppressor cells.
Badger
A M
AM
Department of Immunology, Smith Kline and French Laboratories, Philadelphia, PA 19101.
DiMartino
M J
MJ
Swift
B A
BA
Mirabelli
C K
CK
D000818:Animals; D001169:Arthritis, Experimental / Q000517:prevention & control; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D005260:Female; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013141:Spiro Compounds / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D007166:Immunosuppressive Agents; D009942:Organometallic Compounds; D013141:Spiro Compounds; C026818:spirogermanium