Learned immunosuppressive placebo responses in renal transplant patients

Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4223-4227. doi: 10.1073/pnas.1720548115. Epub 2018 Apr 2.


Patients after organ transplantation or with chronic, inflammatory autoimmune diseases require lifelong treatment with immunosuppressive drugs, which have toxic adverse effects. Recent insight into the neurobiology of placebo responses shows that associative conditioning procedures can be employed as placebo-induced dose reduction strategies in an immunopharmacological regimen. However, it is unclear whether learned immune responses can be produced in patient populations already receiving an immunosuppressive regimen. Thus, 30 renal transplant patients underwent a taste-immune conditioning paradigm, in which immunosuppressive drugs (unconditioned stimulus) were paired with a gustatory stimulus [conditioned stimulus (CS)] during the learning phase. During evocation phase, after patients were reexposed to the CS, T cell proliferative capacity was significantly reduced in comparison with the baseline kinetics of T cell functions under routine drug intake (ƞp2 = 0.34). These data demonstrate, proof-of-concept, that learned immunosuppressive placebo responses can be used as a supportive, placebo-based, dose-reduction strategy to improve treatment efficacy in an ongoing immunopharmacological regimen.

Keywords: T cells; conditioning; immunosuppression; placebo; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Affect
  • Association
  • Catecholamines / metabolism
  • Conditioning, Classical*
  • Cyclosporine / administration & dosage*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Immunologic
  • Female
  • Hemodynamics
  • Humans
  • Hydrocortisone / metabolism
  • Immunosuppressive Agents / administration & dosage*
  • Interferon-gamma Release Tests
  • Kidney Transplantation*
  • Learning
  • Lymphocyte Activation* / drug effects
  • Male
  • Middle Aged
  • Placebo Effect*
  • Placebos
  • Proof of Concept Study
  • T-Lymphocyte Subsets / immunology*
  • Tacrolimus / administration & dosage*
  • Taste


  • Catecholamines
  • Immunosuppressive Agents
  • Placebos
  • Cyclosporine
  • Hydrocortisone
  • Tacrolimus