CELLULAR IMMUNITY IN DEPRESSIVE ILLNESS

中枢神经系统和免疫系统密切相关。 动物模型和人体研究都表明，压力会干扰 免疫调节 我们之前报道过，重度抑郁症是 与自然杀伤（NK）细胞活性降低相关， 细胞免疫参数。 我们的数据还表明皮质醇 在许多重度抑郁症患者中， 仅仅解释了抑郁症患者的免疫抑制。 在本应用中，我们建议扩展免疫的表征 抑郁症患者的情绪失调，并研究可能的 这些患者的免疫抑制机制 首先，我们将进行 免疫学研究，以探索免疫抑制的机制， 细胞和分子水平。 这些包括淋巴细胞表面标志物 细胞毒性和抑制细胞活性的分析、研究、 靶向结合和再循环能力以及淋巴因子产生。 第二、 我们将进行神经内分泌研究，重点是下丘脑- 垂体-肾上腺（HPA）轴，以1）探索 ACTH β-内啡肽和/或皮质醇分泌和特异性免疫措施 在24小时内;和2）评估绵羊促肾上腺皮质激素的作用 静脉注射释放激素（oCRH）对神经内分泌的影响 和免疫功能。 最后，我们将比较神经内分泌免疫 具有不同水平HPA的三组受试者的相互作用 激活：1）抑郁症患者，2）库欣综合征患者; （3）正常对照组。 对抑郁症患者免疫调节的认识 疾病和库欣综合征将提高我们对 大脑和免疫系统之间的相互作用以及 HPA轴的活动在这些相互作用中起作用。

The central nervous system and the immune system are closely interrelated. Both animal models and human studies have shown that stress interferes with immune regulation. We have earlier reported that major depression is associated with a reduction in Natural Killer (NK) cell activity, a parameter of cellular immunity. Our data also suggest that cortisol levels, which are increased in many patients with major depression, cannot solely explain the immunosuppression observed in depressed patients. In this application, we propose to extend the characterization of immune dysregulation in patients with major depression and to study possible mechanisms of immunosuppression in these patients. First, we will conduct immunological studies to explore mechanisms of immunosuppression at the cellular and molecular levels. These include lymphocyte surface marker analyses, studies of cytotoxic and suppressor cell activities, assays of target binding and recycling capacity, and lymphokine production. Second, we will conduct neuroendocrine studies focusing on the hypothalamic- pituitary-adrenal (HPA) axis to 1) explore possible correlations between ACTH beta-endorphin and/or cortisol secretion and specific immune measures over a 24-hour period; and 2) assess the effects of ovine Corticotropin Releasing Hormone (oCRH) given intravenously on neuroendocrine secretion and immune function. Last, we will compare neuroendocrine-immune interactions in three groups of subjects with varying levels of HPA activation: 1) depressed patients; 2) patients with Cushing's syndrome; and 3) normal controls. A better understanding of immune regulation in patients with depressive illness and Cushing's syndrome will enhance our knowledge of the interactions between the brain and the immune system and the possible role that HPA axis activity plays in these interactions.