Prevention of diabetes and induction of non-specific suppressor cell activity in the BB rat by an immunomodulatory azaspirane, SK&F 106610

Journal of Autoimmunity
A RabinovitchA M Badger

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 ce...Continue Reading

Citations

Jun 23, 2005·British Journal of Cancer·M Amit-VazinaZ Estrov
Jun 5, 2014·BioMed Research International·Sezin OzerNihan Gonulol
Dec 7, 2007·Operative Dentistry·Sérgio Kiyoshi IshikiriamaJosé Mondelli
Jun 29, 2006·Operative Dentistry·Soon-Young Lee, Sung-Ho Park
Aug 17, 1999·Toxicology and Applied Pharmacology·J A HandlerP J Bugelski

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