PSYCONEUROIMMUNE INTERACTIONS IN IMMUNOSUPPRESSION

免疫抑制中的心理神经免疫相互作用

• 批准号: 2248947
• 负责人: EDWARD L. MORGAN
• 金额: $ 15.88万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2248947
• 关键词: B lymphocyte; T lymphocyte; antibody formation; cell differentiation; cytokine; flow cytometry; hormone receptor; hormone regulation /control mechanism; human tissue; immunoglobulin G; immunosuppression; inhibitor /antagonist; leukocyte activation /transformation; monocyte; nucleic acid hybridization; peptide hormone; protein biosynthesis; psychoneuroimmunology; receptor expression; stimulant /agonist; tissue /cell culture

The bi-directional communication between the central nervous system and other organ systems is a critical event for the maintenance of mental and physical health. An example of such a communication is the interaction between the neuroendocrine and immune systems. Evidence for this psychoneuro-immune interaction is derived from studies showing that neuroendocrine hormones regulate in vivo and in vitro immune function. Neuroendocrine hormones are thought to be in involved in immunological abnormalities associated with; drug addiction, post traumatic stress syndrome, and more recently acquired immunodeficiency syndrome (AIDS) Acute stress is known to activate corticotropin-releasing factor which induces the anterior lobe of the pituitary gland to release opioid peptide hormones in quantities sufficient to suppress humoral and cell- mediated immunity in both man and animals. In addition to neuroendocrine production of opioid peptides, cells of the immune system are reported to synthesize opioid-like peptides. Thus, neuroendocrine production, the potential de novo synthesis of opioid peptides by cells of the immune system, and their known regulatory action within the immune microenvironment suggest that neuroendocrine peptide hormones may form part of an autocrine/paracrine regulatory network for the control of lymphocyte activation. Immunosuppression associated with immunodeficiency states may be due in part to aberrant activation of this immunoregulatory circuit. The major hypothesis of this proposal is that opioid or opioid-like peptide hormones are involved in the suppression of B lymphocyte differentiation to antibody synthesis. These peptide hormones may suppress antibody synthesis by acting directly on B lymphocytes and/or indirectly by influencing cytokine synthesis/action by monocytes and T lymphocytes. Major questions to be asked are: 1. What is specificity of opioid-receptor interactions in the suppression of antibody synthesis? Opioid specific receptor agonists and antagonists (delta, eta, and kappa) will be assessed for immunoregulatory activity. 2. Do human PBMC (Mo,T, and B cells) express receptors for opioid peptides? The expression of eta, delta, and kappa-specific receptors on stimulated and unstimulated cells will be assessed. 3. What are the mechanisms by which opioid peptides suppress antibody synthesis? Studies will be conducted to determine if opioid peptides suppress: a) the synthesis/action of accessory cytokines; b) synthesis of a specific IgG subclass; c) IgG synthesis at the level of transcription or translation.

中枢神经系统与 其他器官系统是维持心理和 身体健康。 这种交流的一个例子是互动 在神经内分泌和免疫系统之间。 证据 Psychoneuro-rmmune相互作用来自研究表明 神经内分泌激素调节体内和体外免疫功能。 神经内分泌激素被认为参与免疫学 与之相关的异常；吸毒成瘾，创伤后压力 综合征，最近获得的免疫缺陷综合征（AIDS） 已知急性应激会激活皮质激素释放因子，该因子 诱导垂体的前叶释放阿片类药物 肽激素的数量足以抑制体液和细胞 人和动物的介导的免疫力。 除了阿片类肽的神经内分泌产生外， 据报道免疫系统合成阿片类药物样肽。 因此， 神经内分泌生产，阿片类药物的潜在从头合成 通过免疫系统细胞及其已知调节作用的肽 在免疫微环境中表明神经内分泌肽 激素可能构成自分泌/旁分泌调节网络的一部分 淋巴细胞激活的控制。 与之相关的免疫抑制 免疫缺陷状态可能部分归因于异常激活 免疫调节电路。 该提议的主要假设是阿片类药物或阿片类药物样 肽激素参与B淋巴细胞的抑制 与抗体合成的分化。 这些肽激素可能 通过直接作用于B淋巴细胞和/或来抑制抗体合成 通过单核细胞和T的细胞因子合成/作用间接影响 淋巴细胞。 要问的主要问题是： 1。阿片类药物相互作用的特异性是什么 抑制抗体合成？阿片类药物特异性受体激动剂和 拮抗剂（Delta，ETA和Kappa）将进行免疫调节的评估 活动。 2。人PBMC（MO，T和B细胞）表达阿片类药物的受体 肽？ ETA，Delta和Kappa特异性受体的表达 将评估刺激和未刺激的细胞。 3。阿片类肽抑制抗体的机制是什么 合成？ 将进行研究以确定阿片类肽是否 抑制：a）辅助细胞因子的合成/作用； b）合成 特定的IgG子类； c）IgG合成在 转录或翻译。