Spinedi E, Hadid R, Daneva T, Gaillard R C
Neuroendocrine Unit, Multidisciplinary Institute on Cell Biology, La Plata, Argentina.
Neuroendocrinology. 1992 Jul;56(1):46-53. doi: 10.1159/000126207.
Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10(-10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS)
抗原激活的免疫细胞会急性释放细胞因子，这些细胞因子除了对免疫系统有作用外，还会增强下丘脑 - 垂体 - 肾上腺皮质（HPA）功能以对抗炎症过程。本研究旨在利用体外实验范式来测试，免疫系统衍生的不同物质是否存在下丘脑和/或正中隆起作用位点，从而刺激促肾上腺皮质激素释放激素（CRH）和/或精氨酸加压素（AVP）神经元通路。为此，从雌性大鼠身上解剖出整个内侧基底下丘脑（包含正中隆起），并在体外与几种浓度的白细胞介素 -1（IL -1）β、白细胞介素 -6（IL -6）、肿瘤坏死因子（TNF）-α、胸腺素组分5（TF5）或细菌脂多糖（LPS）一起孵育。孵育40分钟后，通过特异性放射免疫测定法（RIAs）测量释放到孵育培养基中的CRH和AVP量。通过用不同测试物质灌注分离的大鼠正中隆起片段进行了额外实验；释放到培养基中的CRH和AVP也通过RIAs测量。结果表明，IL -1β（10^(-11)至10^(-7) M）、IL -6（0.06×10^(-10)至0.4×10^(-10) M）、TNF -α（6×10^(-9)至6×10^(-7) M）和TF5（5 - 500微克/毫升）而非LPS（1 - 100纳克/毫升）以浓度相关的方式显著增强下丘脑CRH分泌至基线以上。此外，灌注实验表明，在所有测试物质中，只有IL -6在正中隆起水平具有直接且剂量依赖性的CRH释放活性。相反，在任何一种体外设计中，均没有制剂增强基础AVP释放。（摘要截断于250字）
