Abstract |
Immunomodulatory azaspirane compounds have immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of action of azaspiranes appears to be the induction of antigen non-specific (natural) suppressor cell activity. In this study, we tested the azaspirane, SK&F 106610 in an animal model of autoimmune ( type 1) diabetes, the BB rat. Oral administration of SK&F 106610 (15 mg/kg/day) to diabetes-prone BB rats, from age 30 days, significantly decreased diabetes incidence at 100 days from 80% (24 of 30 control rats) to 32% (10 of 31 drug-treated rats, P < 0.001). Protection from diabetes by SK&F 106610 was accompanied by decreased lymphocytic infiltration of the pancreatic islets (insulitis). No changes occurred in splenic T cell, B cell or macrophage subsets, or in proliferative responses to the mitogens lipopolysaccharide and concanavalin A (Con-A). Cell mixing experiments in vitro, however, revealed increased antigen non-specific suppressor activity (suppression of splenic lymphoproliferative response to Con-A) in spleens of SK&F 106610-treated rats. The suppressor cell activity was enriched in a low density fraction of splenic cells relatively depleted of T cells, B cells, macrophages and natural killer cells. These results indicate that the azaspirane compound, SK&F 106610 can prevent insulitis and autoimmune diabetes in BB rats and that these actions may be related to the activation of non-specific (natural) suppressor cells.
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Authors | A Rabinovitch, W L Suarez, H Y Qin, R F Power, A M Badger |
Journal | Journal of autoimmunity
(J Autoimmun)
Vol. 6
Issue 1
Pg. 39-49
(Feb 1993)
ISSN: 0896-8411 [Print] England |
PMID | 8457285
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunosuppressive Agents
- Piperidines
- Spiro Compounds
- SK&F 106610
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Topics |
- Administration, Oral
- Animals
- Autoimmune Diseases
(immunology, pathology, prevention & control)
- Diabetes Mellitus, Type 1
(immunology, pathology, prevention & control)
- Female
- Immunophenotyping
- Immunosuppressive Agents
(administration & dosage, therapeutic use)
- Islets of Langerhans
(pathology)
- Lymphocyte Activation
- Lymphocyte Subsets
(immunology)
- Male
- Piperidines
(administration & dosage, therapeutic use)
- Rats
- Rats, Inbred BB
(immunology)
- Spiro Compounds
(administration & dosage, therapeutic use)
- Spleen
(immunology)
- T-Lymphocytes, Regulatory
(immunology)
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