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

内容提要如下：多次小剂量链脲佐菌素(SZ)诱导的胰岛素依赖型糖尿病(IDDM)动物模型是以单核细胞浸润为特征的。抗ICAM-1和抗LFA-1单抗可降低SZ诱导的胰岛素炎症和血糖浓度(参考文献1)。ICAM-1在血管内皮细胞上的表达随胰岛素炎症程度的加重而增加。此外，NZBxNZWF1小鼠是人类系统性红斑狼疮的动物模型，在肾小球肾炎(GN)的发展过程中，中性粒细胞、巨噬细胞、T细胞和表达LFA-1分子的CD4+细胞在肾小球内聚集增加。NZBxNZWF1小鼠表现出与年龄相关的ICAM-1表达的显著增加，与GN的发展相关(参考文献3)。在LDV感染的小鼠中，这些分子的抑制表达与抑制胰岛素炎或GN有关(参考文献1-3)。LDV感染小鼠的这种抑制作用可能不是由于巨噬细胞产生IL-6的改变(参考文献4)。另一方面，呼肠孤病毒2型诱导的乳鼠糖尿病样综合征被认为是人类IDDM的另一种动物模型。抗ICAM-1和LFA-1的单抗治疗可以预防糖耐量异常的胰岛素炎的发展(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