NEUROENDOCRINE/IMMUNE INTERACTIONS: ROLE OF MELATONIN

神经内分泌/免疫相互作用：褪黑激素的作用

• 批准号: 6041782
• 负责人: STEVEN M YELLON
• 金额: $ 26.77万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-20 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6041782
• 关键词: cell mediated lymphocytolysis test; circadian rhythms; flow cytometry; gene rearrangement; hamsters; hormone regulation /control mechanism; immunoglobulin genes; immunoregulation; melatonin; neuroimmunomodulation; photostimulus; pineal body; seasons

DESCRIPTION (applicant's abstract): Physiological adaptations anticipate and coincide with changes in season. Failures to adapt are associated with increased incidence of disease, mortality and mental dysfunctions that include seasonal affective disorders and depression. Day length is the primary environmental cue that regulates a variety of physiological adaptations that anticipate seasonal challenges. Preliminary studies indicate that day length selectively regulates immune functions in the Siberian hamster, a seasonal breeding species in which the mechanism that controls physiological adaptations to day length has been extensively studied. Hamsters in short days (analogous to winter) had increased numbers of leukocytes, T helper cells and eosinophils; natural killer cell cytolytic activity and spontaneous lymphoblastogenesis were also enhanced. In contrast, other indices of immune cell functions were reduced, including T cell-dependent antibody production, as well as phagocytosis and oxidative burst activities by granulocytes and monocytes. Since the neuroendocrine system that mediates the influence of day length on seasonal reproductive physiology involves the circadian pineal melatonin rhythm, the major focus of the proposal is to test the hypothesis that the pineal melatonin rhythm mediates photoperiod control of innate and adaptive immune system functions. An integrative approach to this hypothesis is based upon assessment of the magnitude and tempo of immune responses to changes in day length. The possibility that daily rhythms in immune cell functions are driven by changes in specific immunophenotypes will be addressed. To determine whether photoperiod effects on immune functions depend on the melatonin rhythm, hamsters will be pinealectomized and administered timed treatments to replace specific aspects of the melatonin rhythm. Measures were developed for this seasonal animal model to assess multiple immune system indices by highly sensitive and sophisticated flow cytometry methods for phenotyping, cell-mediated cytolysis, antibody isotype switching and phagocytic cell function. Regulation of specific immune system parameters by photoperiod may potentiate disease resistance, promote adaptations to seasonal challenges in the environment, and provide the foundation to address the therapeutic value of such treatments to selectively modulate immune function in other species. Fundamental knowledge of circadian time keeping and neuroimmune interactions may lead to development of novel approaches to maximize immune responsiveness or slow the deterioration of immune system function that is associated with immunodeficiency, autoimmunity, sleep disturbances, aging and seasonality in behavioral disorders.

描述（申请人的摘要）：生理适应预期和 与季节变化相吻合。未能适应与以下因素有关： 疾病、死亡率和精神功能障碍的发生率增加，包括 季节性情感障碍和抑郁症。日照长度是首要因素 调节多种生理适应的环境线索 预见季节性挑战。初步研究表明，日照长度 选择性调节西伯利亚仓鼠的免疫功能，这是一种季节性的 控制生理适应机制的育种物种 日长已被广泛研究。仓鼠在短日内（类似 到冬天）白细胞、辅助性 T 细胞和嗜酸性粒细胞数量增加； 自然杀伤细胞的溶细胞活性和自发性淋巴母细胞生成 也增强了。相比之下，免疫细胞功能的其他指标是 减少，包括 T 细胞依赖性抗体的产生，以及 粒细胞和单核细胞的吞噬作用和氧化爆发活动。 由于神经内分泌系统介导白昼长度的影响 季节性生殖生理学涉及昼夜节律松果体褪黑激素 节奏，该提案的主要重点是检验以下假设： 松果体褪黑激素节律介导先天和适应性的光周期控制 免疫系统功能。该假设的综合方法基于 在评估免疫反应对变化的幅度和速度时 一天的长度。免疫细胞功能的日常节律可能是 由特定免疫表型的变化驱动的问题将得到解决。确定 光周期对免疫功能的影响是否取决于褪黑激素的节律， 仓鼠将被切除松果体并进行定时治疗以取代 褪黑激素节律的具体方面。为此制定了措施 季节性动物模型通过高度评估多种免疫系统指标 用于表型分析的灵敏且复杂的流式细胞术方法， 细胞介导的细胞溶解、抗体同种型转换和吞噬细胞 功能。光周期对特定免疫系统参数的调节可能 增强抗病能力，促进对季节性挑战的适应 环境，并为解决治疗价值提供基础 这种治疗可以选择性地调节其他物种的免疫功能。 昼夜节律计时和神经免疫相互作用的基础知识 可能会导致开发出最大化免疫反应的新方法 或减缓与以下相关的免疫系统功能的恶化 免疫缺陷、自身免疫、睡眠障碍、衰老和季节性 行为障碍。