Shannon E J, Morales M J, Sandoval F
Laboratory Research Branch G.W. Long Hansen's Disease Center, Louisiana State University, Baton Rouge 70894, USA.
Immunopharmacology. 1997 Jan;35(3):203-12. doi: 10.1016/s0162-3109(96)00149-x.
Thalidomide, which has a long history of tragedy because of its ability to cause severe birth defects, is very effective in alleviating erythema nodosum leprosum in leprosy patients and aphthous ulcers in AIDS patients. The causes of these inflammatory diseases and the mechanism by which thalidomide diminishes them are unknown. It has been suggested that modulation of the immune response plays an important role. We found that thalidomide exerts immunomodulatory activity in three bioassays. It suppresses an IgM plaque forming cell response in mice injected with sheep erythrocytes: it inhibits TNF-alpha production by LPS stimulated human mononuclear cells: and it enhances IL-2 production by Con-A stimulated human mononuclear cells. We employed these bioassays to compare the activity of 15 analogs of thalidomide with thalidomide itself. Eight of the compounds were derivatives of the glutarimide moiety of thalidomide and the others were phthalimide or derivatives of the phthalimide moiety of thalidomide. N-hydroxyphthalimide, a simple derivative of phthalimide, was more effective than thalidomide and was also the most effective of the compounds assayed in suppressing the IgM plaque and TNF-alpha responses, but it did not enhance the IL-2 response, instead, it significantly suppressed it.
沙利度胺因能导致严重出生缺陷而有着悠久的悲剧历史，但它在减轻麻风病人的麻风结节性红斑和艾滋病患者的阿弗他溃疡方面非常有效。这些炎症性疾病的病因以及沙利度胺减轻它们的机制尚不清楚。有人提出免疫反应的调节起着重要作用。我们发现沙利度胺在三种生物测定中发挥免疫调节活性。它抑制注射绵羊红细胞的小鼠中的IgM斑块形成细胞反应；它抑制脂多糖刺激的人单核细胞产生肿瘤坏死因子-α；它增强刀豆蛋白A刺激的人单核细胞产生白细胞介素-2。我们采用这些生物测定来比较沙利度胺的15种类似物与沙利度胺本身的活性。其中8种化合物是沙利度胺戊二酰亚胺部分的衍生物，其他的是邻苯二甲酰亚胺或沙利度胺邻苯二甲酰亚胺部分的衍生物。邻苯二甲酰亚胺的一种简单衍生物N-羟基邻苯二甲酰亚胺比沙利度胺更有效，并且在抑制IgM斑块和肿瘤坏死因子-α反应方面也是所测定化合物中最有效的，但它没有增强白细胞介素-2反应，反而显著抑制了它。
