Karalis K, Mastorakos G, Chrousos G P, Tolis G
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1994 May;93(5):2000-6. doi: 10.1172/JCI117193.
Somatostatin (Sms) and its agonist analogues inhibit the secretory activities of endocrine and neural cells. Recent studies have suggested that Sms has significant immunomodulatory properties. In this study, we examine the effects of two Sms octapeptide analogues on the inflammatory reaction in vivo. BIM 23014 (Somatulin) and Sandostatin were administered to male Sprague-Dawley rats subject to carrageenin-induced aseptic inflammation, at doses of 2-10 micrograms/rat, given either systemically or locally. Animals were killed 7 h after the induction of the inflammation, and the inflammatory exudates were aspirated and quantitated in terms of volume and leukocyte concentration. Sms analogues, administered via either route, significantly reduced the volume and the leukocyte concentration of the exudate in a time- and dose-dependent fashion. In corroboration of these, immunohistochemical evaluation of the levels of local inflammatory mediators, such as immunoreactive (Ir) TNF-alpha, Irsubstance P, and Ircorticotropin-releasing hormone, was inhibited significantly by Sms analogue treatment. These findings suggest that Sms analogues have significant antiinflammatory effects in vivo, associated with suppression of proinflammatory cytokines and neuropeptides. Furthermore, these data suggest that Sms agonists may be useful in the control of inflammatory reaction.
生长抑素（Sms）及其激动剂类似物可抑制内分泌细胞和神经细胞的分泌活动。最近的研究表明，Sms具有显著的免疫调节特性。在本研究中，我们检测了两种Sms八肽类似物对体内炎症反应的影响。将BIM 23014（生长抑素）和善得定给予因角叉菜胶诱导产生无菌性炎症的雄性Sprague-Dawley大鼠，剂量为2-10微克/大鼠，通过全身或局部给药。在炎症诱导7小时后处死动物，抽取炎性渗出物，并对其体积和白细胞浓度进行定量。通过两种途径给药的Sms类似物均以时间和剂量依赖性方式显著降低了渗出物的体积和白细胞浓度。与此相符的是，Sms类似物治疗显著抑制了局部炎症介质水平的免疫组织化学评估，如免疫反应性（Ir）肿瘤坏死因子-α、IrP物质和Ir促肾上腺皮质激素释放激素。这些发现表明，Sms类似物在体内具有显著的抗炎作用，与促炎细胞因子和神经肽的抑制有关。此外，这些数据表明，Sms激动剂可能有助于控制炎症反应。
