ENDOCRINE-IMMUNE-REPRODUCTIVE SYSTEM INTERACTIONS

该项目的目的是增加我们的 了解内分泌和 实验动物和人类的免疫系统。几 免疫系统产物，如炎性细胞因子， 肿瘤坏死因子-a、白细胞介素-1和白细胞介素-6激活 下丘脑-垂体-肾上腺（HPA）轴和通过它 抑制和抑制炎症/免疫反应。 白细胞介素-6在人体中特别有效，不仅刺激 促肾上腺皮质激素和皮质醇，以及精氨酸加压素（AVP）分泌。 IL-6导致严重疲劳和嗜睡。血浆白细胞介素-6 在糖皮质激素缺乏状态和运动后升高。 血浆IL-6和TNF α也在过度炎症性疾病中升高。 白天嗜睡白细胞介素-6在感染性， 炎症和创伤状态可以解释 AVP分泌异常综合征 states.我们最近证明，促肾上腺皮质激素释放 激素（CRH）在炎症部位局部产生， 在自分泌/旁分泌水平上具有显著的促炎作用。 我们称之为“免疫”CRH。糖皮质激素和 生长抑素抑制，RU 486显著增加局部 在炎症部位分泌免疫CRH。CRH是一种有效的 肥大细胞的脱髓鞘，这种现象可以被抑制， 非肽类CRH拮抗剂，对1型受体特异，称为 安他拉明免疫CRH在卵巢和子宫内膜中有表达 它可能参与炎症现象， 排卵、黄体溶解、胚泡着床和月经。 类风湿关节炎患者的垂体-肾上腺功能有缺陷， 轴对炎症刺激的反应并产生过度的 大量的免疫CRH。患者 多发性硬化症有轻度皮质醇增多症，这是持续的， 慢性下丘脑AVP而不是CRH分泌过多。的 人CRH基因含有雌激素反应元件， 启动子区提供了解释性的 自身免疫性/炎症性疾病发病率的二型性。 CRH拮抗剂可用于治疗 自体免疫/炎性疾病。压力荷尔蒙皮质醇 和儿茶酚胺抑制白细胞介素-12和/或刺激 人巨噬细胞中的白细胞介素-10，导致Thelper转移 体液免疫的类型。观察到相同的效果， 组胺和P物质。

The purpose of this project is to increase our understanding of the interactions between the endocrine and immune systems in both experimental animals and humans. Several immune system products, such as the inflammatory cytokines, Tumor Necrosis Factor-a, Interleukin-1, and Interleukin-6 activate the hypothalamic-pituitary-adrenal (HPA) axis and through it suppress and restrain the inflammatory/immune response. Interleukin-6 is particularly potent in humans, stimulating not only ACTH and cortisol but also arginine-vasopressin (AVP) secretion. IL-6 causes profound fatigue and somnolence. Plasma interleukin-6 is elevated in glucocorticoid deficiency states and after exercise. Plasma IL-6 and TNFa are also elevated in disorders of excessive daytime sleepiness. Elevations of interleukin-6 in infectious, inflammatory, and traumatic states may explain the pathogenesis of the Syndrome of Inappropriate AVP Secretion observed in these states. We recently demonstrated that corticotropin-releasing hormone (CRH) is produced localy at sites of inflammation and has profound pro-inflammatory effects at an autocrine/paracrine level. We have called this "immune" CRH. Glucocorticoids and somatostatin suppress, and RU 486 markedly augments local secretion of immune CRH at an inflammatory site. CRH is a potent degranulator of mast cells, a phenomenon that can be inhibited by a nonpeptide CRH antagonist, specific for type 1 receptors called antalarmin. Immune CRH was found in the ovary and endometrium where it may participate in the inflammatory phenomena of ovulation, luteolysis, blastocyst implantation, and menstuation. Patients with rheumatoid arthritis have defective pituitary-adrenal axis responses to inflammatory stimuli and produce excessive amounts of immune CRH in their inflamed joints. Patients with multiple sclerosis have mild hypercortisolism, which is sustained by chronic hypothalamic AVP rather than CRH hypersecretion. The human CRH gene contains estrogen-responsive elements it its promoter region providing an explanation for the sexual dimorphism in the incidence of autoimmune/inflammatory disease. CRH antagonists may be useful in the treatment of autommune/inflammatory diseases. The stress hormones cortisol and catecholamines suppress interleukin-12 and/or stimulate interleukin-10 in human macrophages, causing a shift of the Thelper type towards humoral immunity. The same effect is observed with histamine and substance P.