Induction of Non-Specific Suppressor Cells in Normal Lewis Rats by a Novel Azaspirane SK&F 105685

SK&F 105685 (N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2- propanamine dihydrochloride) is a novel azaspirane which has therapeutic activity in rat models of autoimmune disease. In this study, we have demonstrated that SK&F 105685 is a potent inducer of non-specific suppressor cells (SC). Oral administration of 15-30 mg/kg/day results in the generation of SC in the spleen, lymph nodes and bone marrow, but not the thymus of Lewis rats. Splenic SC suppress Con-A-induced proliferation in co-culture assays at effector-responder ratios of 1:1 to 1:64. SC are radiation resistant (2000 R), non-T, non-B cells, partially adherent to plastic surfaces and are enriched in a 1.07 g/ml fraction of a Percoll density gradient. Their activity is increased, rather than ablated, by indomethacin. No definitive changes in Ig+, OX-19+, OX-8+, W3/25+ or asialo GM1+ cells could be detected in the spleens of treated rats compared to control untreated animals. Elevated levels of both radiation-sensitive and radiation-resistant suppressor cells were found in the bone marrow of treated rats in addition to the radiosensitive SC normally present in this tissue.