EFFECT OF FUSIDIC ACID ON INTERLEUKIN-1 (IL-1)-INDUCED AND IL-6-INDUCED PANCREATIC BETA-CELL FUNCTIONS IN RATS
EFFECT OF FUSIDIC ACID ON INTERLEUKIN-1 (IL-1)-INDUCED AND IL-6-INDUCED PANCREATIC BETA-CELL FUNCTIONS IN RATS
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DOI：
10.1677/joe.0.1320345
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发表时间：
1992-03-01
影响因子：
4
通讯作者：
BUSCHARD, K
中科院分区：
文献类型：
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作者：
BENDTZEN, K;DIAMANT, M;BUSCHARD, K
夫西地酸及其钠盐（夫西定）是具有甾体一级结构的抗葡萄球菌药物。这两种化合物都显示出以与环孢菌素A类似的方式阻止细胞因子白细胞介素（IL）-1和IL-6的淋巴细胞共刺激活性。如本文所示，夫西定还可以阻止人重组IL-1-β（rIL-1-β）的抑制作用和人rIL-6对正常大鼠胰岛体外葡萄糖诱导的胰岛素产生的刺激作用。该药物还抑制rIL-1-β诱导的胰岛产生IL-6。Fusidin在3 - 30 μ g/ml的浓度范围内表现出剂量相关效应，并且当在rIL-1-β后1、4和24小时加入时，该药物的活性逐渐降低。电子显微镜研究表明，与rIL-1-β培养72小时的β-细胞积累较少的脂质的存在下，梭菌素，最可能反映了功能保护作用的药物。然而，rIL-1-β诱导的β细胞的其他特征性超微结构变化没有改变。研究表明，梭菌素可能在临床上有效地调节IL-1和IL-6诱导的β细胞功能变化。
Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs with a steroidal primary structure. Both compounds have been shown to prevent the lymphocyte co-stimulatory activities of the cytokines, interleukin (IL)-1 and IL-6, in a manner similar to that of cyclosporin A. As shown in this paper, fusidin also prevents the inhibitory effect of human recombinant IL-1-beta (rIL-1-beta) and the stimulatory effect of human rIL-6, on glucose-induced insulin production in vitro by normal rat pancreatic islets. The drug also inhibited rIL-1-beta-induced IL-6 production by the islets. Fusidin showed a dose-related effect at pharmacologically relevant concentrations from 3 to 30-mu-g/ml, and the drug was progressively less active when added 1, 4 and 24 h after rIL-1-beta. Electron microscopical studies showed that beta-cells cultured for 72 h with rIL-1-beta accumulated less lipid in the presence of fusidin, most probably reflecting the functionally protective effect of the drug. Other characteristic ultrastructural changes induced in beta-cells by rIL-1-beta were, however, not altered. It is suggested that fusidin may prove clinically effective as a modulator of IL-1- and IL-6-induced changes in beta-cell functions.