STRESS AXIS, IMMUNE SYSTEM-DERIVED CYTOKINES AND ETHANOL

乙醇(ET)的消费改变了某些监管方面的 下丘脑-垂体-肾上腺轴(HPAA)。因为它的完整性 这一系统依赖于协调合成和分泌 下丘脑的特定调节物质(例如，促肾上腺皮质激素- 促肾上腺皮质激素释放激素(CRH)；加压素(AVP)；生物胺 腺体(例如，β-内啡肽(BE)；ACTH)和肾上腺(例如， 儿茶酚胺；糖皮质激素)水平，我们一直在评估 ET对HPAA各层级的影响。激活HPAA或 短期和长期服用ET都伴随着皮质醇增多症 和ET戒断综合征。酗酒者通常会出现一种伪装- 库欣综合征，约17%-40%的酗酒者 对地塞米松抑制试验的反应在第一周 禁欲。由于糖皮质激素升高的相对状态(慢性 连续性或慢性间歇性)可导致神经改变，甚至 细胞死亡，特别是在海马体中，进行性丧失 许多酗酒者的认知能力确实可能部分归因于 高皮质醇血症和随后不可逆转的神经损伤 海马体和中枢神经系统的其他区域。此外， 配备了双向通信的概念， HPAA和免疫系统，我们正在探索是否确定 免疫系统衍生的细胞因子可能正在改善或加速 通过内分泌或旁分泌作用导致的神经死亡。当然是细胞因子 刺激不同类型的细胞试图修复细胞损伤 通过细胞内信号放大，可以与 ET和糖皮质激素过度刺激选定的神经群体 导致他们的灭亡。

Consumption of ethanol (Et) alters certain regulatory aspects of the hypothalamic-pituitary-adrenal axis (HPAA). Because the integrity of this system depends on the coordinated synthesis and secretion of specific regulatory substances at the hypothalamic (e.g., corticotropin- releasing hormone (CRH); vasopressin (AVP); biogenic amines), pituitary- gland (e.g., beta endorphin (BE); ACTH) and adrenal gland (e.g., catecholamines; glucocorticoids) level, we have been evaluating the impact of Et at each level of the HPAA. Activation of the HPAA or hypercortisolism accompanies both short- and long-term consumption of Et and the Et withdrawal syndrome. Alcoholics often present with a pseudo- Cushing's syndrome in which some 17-40 percent of alcoholics do not respond to the dexamethasone suppression test during the first week of abstinence. Since a relative state of elevated glucocorticoids (chronic continuous or chronic intermittent) can lead to neural changes and even cell death, particularly in the hippocampus, the progressive loss of cognitive capacity in many alcoholics may indeed be due in part to hypercortisolemia and subsequent irreversible neural damage in the hippocampus and other areas of the central nervous system. Furthermore, armed with the concept of the bidirectional communication between the HPAA and the immune system, we are exploring whether or not certain immune system-derived cytokines may be ameliorating or accelerating neural death through endocrine or paracrine actions. Certainly cytokines stimulate diverse cell types in an attempt to repair cellular damage through intracellular signal amplification which could in concert with Et and glucocorticoids overstimulate selected neural populations leading to their demise.