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

本文综述了以下五篇文献。多次低剂量链脲佐菌素（SZ）诱导的胰岛炎是一种以单核细胞浸润为特征的人胰岛素依赖型糖尿病（IDDM）动物模型。SZ诱导的胰岛炎和血糖浓度通过抗ICAM-1和抗LFA-1单克隆抗体治疗降低（参考文献1）。血管内皮细胞ICAM-1表达随胰岛炎程度的加重而增加。此外，NZBxNZWF 1小鼠，这是一种人类系统性红斑狼疮的动物模型，显示在<plus-minus>肾小球肾炎（GN）的发展过程中，肾小球内表达LFA-1分子的中性粒细胞、巨噬细胞、T细胞和CD 4细胞的积累增加。NZBxNZWF 1小鼠表现出与GN发生相关的ICAM-1表达的年龄相关性和显著增加（参考文献3）。在LDV感染的小鼠中，这些分子的表达抑制与胰岛炎或GN的抑制有关（参考文献1 -3）。LDV感染小鼠中的这种抑制作用可能不是由于巨噬细胞产生的IL-6改变所致（参考文献4）。另一方面，哺乳DBA/1小鼠中呼肠孤病毒2型诱导的糖尿病样综合征被认为是人IDDM的另一种动物模型。用抗ICAM-1和LFA-1的单克隆抗体治疗可预防葡萄糖耐量异常的胰岛炎的发生（参考文献5）。总之，我们的观察表明这些抗体在某些自身免疫性疾病中具有潜在的治疗应用

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