Neurobehavioral mechanisms of learned immunosuppressive placebo responses: from basics towards clinical application

习得免疫抑制安慰剂反应的神经行为机制：从基础知识到临床应用

• 批准号: 188177368
• 负责人: Professor Dr. Manfred Schedlowski
• 金额: --
• 依托单位: Institut für Medizinische Psychologie und Verhaltensimmunbiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/188177368?language=en
• 关键词: Neurobehavioral; mechanisms; learned; immunosuppressive; placebo

We have established a model of behaviorally conditioned placebo effects of immune functions in healthy humans by demonstrating a behaviorally conditioned suppression of T cell proliferation and cytokine production (IL-2, -IFN). Based on this experimental data, the potential clinical feasibility of behaviorally conditioned immunosuppression will be further analyzed in healthy humans and kidney transplant patients. We shall investigate whether and to what extent the extinction of conditioned suppression of T cell functions and cytokine production can be inhibited via inducing a re-consolidation process in the immune response by treating subjects during the retrieval process with sub-/ low-therapeutic dosages of the calcineurin-inhibitor cyclosporin A. We will also explore whether the learned immunosuppressive placebo response is affected by prior exposure to the unconditioned stimulus cyclosporine A. We will further analyze the effects of conditioned immune changes on the circadian kinetics of immunosuppression in kidney transplant patients under regular immunosuppressive regimen. Finally, the intra-cellular processes of behaviorally conditioned calcineurin inhibition in human peripheral CD4+ T cells will be analyzed. This work will provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system- immune system communication by learned placebo effects.

我们通过证明行为条件抑制T细胞增殖和细胞因子产生（IL-2, -IFN），建立了健康人免疫功能的行为条件安慰剂效应模型。基于这些实验数据，我们将进一步分析行为条件免疫抑制在健康人及肾移植患者中的潜在临床可行性。我们将研究通过在检索过程中使用亚/低剂量的钙调磷酸酶抑制剂环孢素a治疗受试者，是否以及在多大程度上可以通过诱导免疫反应的再巩固过程来抑制T细胞功能和细胞因子产生的条节性抑制的消失。我们还将探讨习得性免疫抑制安慰剂反应是否受到先前暴露于无条件刺激环孢素a的影响将进一步分析条件免疫改变对常规免疫抑制方案下肾移植患者免疫抑制昼夜动力学的影响。最后，将分析人类外周血CD4+ T细胞中行为条件下钙调磷酸酶抑制的细胞内过程。这项工作将为通过学习安慰剂效应调节神经系统-免疫系统通信来抑制免疫功能的疾病的治疗提供新的治疗方法的基础。