CYTOTOXICITY OF HUMAN PI-7 INTERLEUKIN-1 FOR PANCREATIC-ISLETS OF LANGERHANS
CYTOTOXICITY OF HUMAN PI-7 INTERLEUKIN-1 FOR PANCREATIC-ISLETS OF LANGERHANS
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DOI：
10.1126/science.3086977
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发表时间：
1986-06-20
期刊：
影响因子：
56.9
通讯作者：
SVENSON, M
中科院分区：
文献类型：
--
作者：
BENDTZEN, K;MANDRUPPOULSEN, T;SVENSON, M
活化的单核细胞似乎是自身免疫β细胞破坏导致胰岛素依赖性（1型）糖尿病的重要效应细胞。活化单核细胞（人血液）的条件培养基对离体大鼠和人朗格汉斯胰岛具有细胞毒性。这种细胞毒活性可以通过固定纯化的白细胞介素-1 （IL-1）抗体吸附从粗细胞因子制剂中消除。通过酸洗恢复胰岛抑制活性和IL-1活性（以其对胸腺细胞的致comitogenic effect测定）。纯化的天然IL-1和从主要的pI - 7形式的人IL-1衍生的重组IL-1，一致地抑制胰岛素反应。天然IL-1的pI 6和pI 5形式无效。天然IL-1和重组IL-1在胰岛抑制作用和胸腺细胞刺激活性方面表现出相似的剂量反应。抑制胰岛活性的IL-1浓度在皮摩尔范围内。因此，单核细胞来源的pI - 7 IL-1可能导致胰岛细胞损伤，从而导致胰岛素依赖型糖尿病的发生。
Activated mononuclear cells appear to be important effector cells in autoimmune beta cell destruction leading to insulin-dependent (type 1) diabetes mellitus. Conditioned medium from activated mononuclear cells (from human blood) is cytotoxic to isolated rat and human islets of Langerhans. This cytotoxic activity was eliminated from crude cytokine preparations by adsorption with immobilized, purified antibody to interleukin-1 (IL-1). The islet-inhibitory activity and the IL-1 activity (determined by its comitogenic effect on thymocytes) were recovered by acid wash. Purified natural IL-1 and recombinant IL-1 derived from the predominant pI 7 form of human IL-1, consistently inhibited the insulin response. The pI 6 and pI 5 forms of natural IL-1 were ineffective. Natural and recombinant IL-1 exhibited similar dose responses in their islet-inhibitory effect and their thymocyte-stimulatory activity. Concentrations of IL-1 that inhibited islet activity were in the picomolar range. Hence, monocyte-derived pI 7 IL-1 may contribute to islet cell damage and therefore to the development of insulin-dependent diabetes mellitus.