Abstract |
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.
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Authors | A M Badger, A G King, J E Talmadge, D A Schwartz, D H Picker, C K Mirabelli, N Hanna |
Journal | Journal of autoimmunity
(J Autoimmun)
Vol. 3
Issue 4
Pg. 485-500
(Aug 1990)
ISSN: 0896-8411 [Print] England |
PMID | 2145847
(Publication Type: Journal Article)
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Chemical References |
- Adjuvants, Immunologic
- Spiro Compounds
- SK&F 105685
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Topics |
- Adjuvants, Immunologic
(pharmacology)
- Administration, Oral
- Animals
- Cell Separation
- Lymphocyte Activation
(drug effects)
- Lymphoid Tissue
(cytology, drug effects, immunology)
- Male
- Radiation Tolerance
- Rats
- Rats, Inbred Lew
- Spiro Compounds
(administration & dosage, pharmacology)
- T-Lymphocytes, Regulatory
(drug effects, immunology, radiation effects)
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