Relations between development of insulitis and expression of adhesion molecules in multiple low-dose streptozotocin-treated mice.

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Summary consisted of five papers listed bellow.Multiple low-dose streptozotocin (SZ) -induced insulitis is an animal model for human insulin-dependent diabetes mellitus (IDDM) characterized by a mononuclear cell infiltration. SZ-induced insulitis and blood glucose concentrations were reduced by treatment with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (Ref.1). ICAM-1 expression on vascular endothelial cells increased in parallel to the degree of insulitis. Also NZBxNZWF1 mice, which is an animal model for human systemic lupus erythematosus, showed increased accumulation of neutrophils, macrophages, T and CD4 <plus-minus> cells expressing LFA-1 molecule within glomeruli during the development of glomerulonephritis (GN). The NZBxNZWF1 mice exhibited an age-related and profound increase in ICAM-1 expression associated with the development of GN (Ref.3). In LDV infected mice, suppressed expression of these molecules was related with the suppression of insulitis or GN (Ref.1-3). This suppressive effect in LDV-infected mice may not be due to altered IL-6 production by macrophages (Ref.4). On the other hand, reovirus type 2-induced diabetes-like syndrome in suckling DBA/1 mice is considered to be another animal model for human IDDM.The treatment with monoclonal antibodies against ICAM-1 and LFA-1 prevented the development of insulitis with abnormal glucose tolerance (Ref.5). In conclusion, our observations indicate a potential therapeutic application of these antibodies in certain autoimmune disease