Preserving learned immunosuppressive placebo response: perspectives for clinical application

Akin to other physiological responses, immune functions can be modified through behavioral conditioning as part of a learned placebo response. However, like every learning process, learned immune responses are subject to extinction. We analyzed the extinction of learned immunosuppression in healthy male volunteers, using an established conditioning paradigm with the immunosuppressive drug cyclosporin A (CsA) as unconditioned stimulus (US) and a gustatory stimulus as conditioned stimulus (CS). We observed a learned suppression of T-cell function after two and four reexposures to the CS, which was extinguished after 14 unreinforced CS reexposures. However, administration of "subtherapeutic" CsA dosages together with the CS counteracted the extinction of the learned immunosuppression. These findings provide the basis for a potentially successful implementation of conditioning paradigms as supportive therapy to immunopharmacological regimens in clinical settings. The aim is to reduce the required amount of medication while maximizing the therapeutic outcome for the patient's benefit.