Psychoimmunology

心理免疫学

基本信息

批准号：
7485209
负责人：
ANDREW H MILLER
金额：
$ 17.41万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7485209
关键词：
Acute Adenovirus Vector Adrenal Glands Adult Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antigen-Presenting Cells Anxiety Disorders Area Autoimmune Diseases B-Lymphocytes Behavior Behavioral Blood Blood specimen Brain Brain region CREB1 gene Cardiovascular Diseases Cell physiology Cells Chronic Chronic stress Communicable Diseases Condition Control Animal Corticosterone Corticotropin Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Receptors DNA Binding Data Development Diabetes Mellitus Disease Emotional Endogenous depression Epinephrine Exposure to Foundations Functional disorder Genes Genetic Glucocorticoid Receptor HPSE gene Health Homeostasis Human Hydrocortisone Immune Immune System Diseases Immune response Immune system Immunologics Individual Inflammation Inflammatory Interleukin-1 Interleukins Laboratory Animals Lead Life Life Stress Macaca mulatta Maintenance Major Depressive Disorder Malignant Neoplasms Maternal Deprivation Measurement Measures Mediating Mediator of activation protein Medical Messenger RNA Metabolic Diseases Methoxyhydroxyphenylglycol Mitogen-Activated Protein Kinase 3 Modeling Monkeys Natural Killer Cells Nervous system structure Neuraxis Neurobiology Neuropeptides Neurosecretory Systems Norepinephrine Numbers Pathway interactions Patients Peptides Pituitary Gland Play Predisposition Production Proteins Psychosocial Stress Rattus Receptor Signaling Regulation Research Personnel Response Elements Role Secondary to Sexual abuse Signal Pathway Signaling Molecule Speech Spleen Stress Sympathetic Nervous System Syndrome System Testing Trier Social Stress Test Tumor Necrosis Factor-alpha Woman animal facility cytokine day experience exposed human population human TNF protein hypothalamic-pituitary-adrenal axis immune function infancy insight lymphocyte proliferation maternal separation mature animal men nonhuman primate novel peripheral blood physical abuse postnatal programs psychoimmunology receptor receptor downregulation response social stressor transcription factor vector young adult

项目摘要

Numerous studies have indicated that interactions between the central nervous system (CNS) and the immune system play an important role in the maintenance of homeostasis and the development of immunologic diseases including infectious diseases, cancer and autoimmune disorders. One of the most well established findings in the area of CNS-immune interactions is the profound impact of acute and chronic stress on the immune response. Relevant pathways mediating these effects of stress on the immune system include the pothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Given that HPA axis and SNS outflow pathways during stress are regulated by corticotropin releasing factor (CRF), a number of studies have focused on the impact of CRF on the immune system. Interestingly, in addition to causing suppression of both cell-mediated and humoral immune function, CRF has been found to induce the release of several cytokines including (IL) interleukin-1 and -6. These cytokines in turn have been shown to stimulate CRF production/release and mediate a host of behavioral responses that include "sickness behavior" with features that overlap with major depression. Early life stress in humans and laboratory animals has been shown to increase CRF synthesis and secretion and moreover, that CRF pathways are sensitized to subsequent stressor exposure in adulthood. In view of the effect of CRF on the immune system and the potential impact of the immune system on the CNS and CRF, in particular, examination of the potential consequences and contributions of CRF-immune interactions to physical and emotional health in individuals exposed to early life stress is of paramount importance. The long term objectives of this proposed project are to further understand 1) how early life stress impacts upon the adult immune system, 2) whether CRF is the major mediator of the observed effects and 3) whether proinflammatory cytokines contribute to the neurobiologic and immunologic features of early life stress. The hypotheses are that 1) early life stress in laboratory animals (rats and rhesus monkeys) and humans will potentiate stress-induced suppression of cellular and humoral immune responses, 2) early life stress will enhance stress-induced activation of proinflammatory cytokines and their signaling pathways, including NFkB and MAP kinase, 3) enhanced suppression of cellular and humoral immune responses and increased activation of proinflammatory signaling pathways secondary to early life stress will be mediated by CRF and its effects on the HPA axis and/or SNS, and 4) activation of proinflammatory signaling pathways by IL-1 and IL-6 will contribute to the neuroendocrine, behavioral and immunologic manifestations of early life stress. Taken together, these studies will provide new insights into the pathophysiology of early life stress and provide a foundation for the development of novel treatment strategies for the neurobiologic and immunologic consequences of early life stress.

大量研究表明，中枢神经系统（CNS）和免疫系统之间的相互作用在维持体内平衡和免疫疾病（包括传染病、癌症和自身免疫性疾病）的发展中发挥着重要作用。中枢神经系统-免疫相互作用领域最明确的发现之一是急性和慢性应激对免疫反应的深远影响。介导应激对免疫系统影响的相关途径包括丘脑-垂体-肾上腺 (HPA) 轴和交感神经系统 (SNS)。鉴于应激期间的 HPA 轴和 SNS 流出途径受到促肾上腺皮质激素释放因子 (CRF) 的调节，许多研究都集中在 CRF 对免疫系统的影响上。有趣的是，除了抑制细胞介导的免疫功能和体液免疫功能外，还发现 CRF 还能诱导多种细胞因子的释放，包括 (IL) 白介素-1 和 -6。这些细胞因子反过来又被证明可以刺激 CRF 的产生/释放，并介导一系列行为反应，包括具有与重度抑郁症重叠特征的“疾病行为”。人类和实验动物的早期生活压力已被证明会增加 CRF 的合成和分泌，而且 CRF 途径对成年后的压力源暴露敏感。鉴于 CRF 对免疫系统的影响以及免疫系统对 CNS 和 CRF 的潜在影响，特别是检查 CRF 免疫相互作用对早期暴露于 CRF 的个体的身体和情绪健康的潜在后果和贡献。生活压力至关重要。长期目标该拟议项目的目的是进一步了解 1) 早期生活压力如何影响成人免疫系统，2) CRF 是否是观察到的影响的主要介质，3) 促炎细胞因子是否有助于早期生活压力的神经生物学和免疫学特征。假设：1) 实验动物（大鼠和恒河猴）和人类的早期生活压力将增强压力诱导的细胞和体液免疫反应抑制，2) 早期生活压力将增强压力诱导的促炎细胞因子及其信号传导的激活通路，包括 NFkB 和 MAP 激酶，3) 增强对细胞和体液免疫反应的抑制，并增加继发于早期生活压力的促炎信号通路的激活，这将由 CRF 及其对 HPA 轴的影响介导和/或 SNS，4) IL-1 和 IL-6 激活促炎信号通路将有助于早期生活压力的神经内分泌、行为和免疫学表现。总而言之，这些研究将为早期生活压力的病理生理学提供新的见解，并为新型药物的开发奠定基础。针对早期生活压力的神经生物学和免疫学后果的治疗策略。