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

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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.