Buschard K, Aaen K, Horn T, Van Damme J, Bendtzen K
Bartholin Institute, Kommunehospitalet, Copenhagen, Denmark.
Autoimmunity. 1990;5(3):185-94. doi: 10.3109/08916939009002977.
The direct in vitro effect of interleukin-6 (IL-6) on pancreatic beta-cells was studied using isolated Lewis rat islets (25/ml/well) precultured for 7 days and then incubated with or without human recombinant IL-6 (rIL-6) or purified human natural IL-6 (nIL-6). Both sources of IL-6 stimulated insulin secretion over a period of 6 days (P less than 0.01), whereas the levels of insulin within the islets were unaffected. At concentrations above 1.5 ng/ml, rIL-6 almost doubled the content of insulin in the supernatants. At an intermediate concentration, 0.5 ng/ml, rIL-6 preserved insulin secretion by islets cocultured with 2 ng/ml of human recombinant interleukin 1 beta (rIL-1 beta) which otherwise inhibited insulin secretion to 60% of islets cultured in medium alone. Electron microscopic studies showed that rIL-6, 1.5 ng/ml, caused beta-cell specific degenerative changes similar to those previously described after treatment with IL-1 beta; i.e. appearance of opaque intracytoplasmic bodies, autophage vacuoles and signs of mitochondrial degeneration. We conclude that human IL-6 stimulates insulin production and secretion in vitro and induces similar ultrastructural changes in beta-cells as does IL-1 beta. IL-6 may be an endogenous mediator of some of the effects on beta-cells ascribed to IL-1.
利用分离的Lewis大鼠胰岛（25个/毫升/孔）进行预培养7天，然后分别在添加或不添加人重组白细胞介素-6（rIL-6）或纯化的人天然白细胞介素-6（nIL-6）的条件下进行孵育，研究白细胞介素-6（IL-6）对胰腺β细胞的直接体外作用。两种来源的IL-6均在6天的时间内刺激了胰岛素分泌（P＜0.01），而胰岛内的胰岛素水平未受影响。当rIL-6浓度高于1.5纳克/毫升时，其使上清液中的胰岛素含量几乎增加了一倍。在中间浓度0.5纳克/毫升时，rIL-6可维持与2纳克/毫升人重组白细胞介素1β（rIL-1β）共培养的胰岛的胰岛素分泌，否则rIL-1β会将胰岛素分泌抑制至单独在培养基中培养的胰岛的60%。电子显微镜研究显示，1.5纳克/毫升的rIL-6会引起β细胞特异性退行性变化，类似于先前在用IL-1β处理后所描述的变化；即出现不透明的胞浆内体、自噬空泡和线粒体变性的迹象。我们得出结论，人IL-6在体外刺激胰岛素产生和分泌，并在β细胞中诱导与IL-1β相似的超微结构变化。IL-6可能是一些归因于IL-1的对β细胞作用的内源性介质。
