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

我们通过证明T细胞增殖和细胞因子产生（IL-2、-IFN）的行为条件抑制，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，将在健康人和肾移植患者中进一步分析行为条件免疫抑制的潜在临床可行性。我们将研究是否以及在何种程度上可以通过诱导免疫应答中的再巩固过程来抑制T细胞功能和细胞因子产生的条件抑制的消退，所述再巩固过程通过在恢复过程中用亚/低治疗剂量的钙调神经磷酸酶抑制剂环孢菌素A治疗受试者来进行。我们还将探讨是否学习免疫抑制安慰剂反应是受先前暴露于非条件刺激环孢素A。我们将进一步分析条件性免疫改变对肾移植患者在常规免疫抑制方案下免疫抑制的昼夜动力学的影响。最后，将分析人外周CD 4 + T细胞中行为条件钙调磷酸酶抑制的细胞内过程。这项工作将为治疗疾病的新治疗方法提供基础，其中需要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。

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.