Conditioned manipulation of natural killer (NK) cells in humans using a discriminative learning protocol

There is growing evidence indicating that the immune function can be modified by classical conditioning techniques. This phenomenon, initially explored in animals, is further documented by studies providing evidence that the human immune response can also be influenced by classical conditioning processes. In the present study, we tested the hypothesis that human immune parameters can be modulated by discriminative learning processes. Using a classical discriminative conditioning design, healthy volunteers were provided with a CS+ (sherbet sweet/white noise), which was repeatedly paired with an injection of epinephrine (unconditioned stimulus, US). After epinephrine injections (0.2 mg subcutaneously), a transient increase of natural killer (NK) cell activity (unconditioned response, UR) could be observed. A second stimulus complex (herbal sweet/auditory stimulus, conditioned stimulus, CS-) remained without reinforcement. After repeated presentation of the stimuli, re-exposure of the CS+ on the test trial 1 resulted in a significantly increased number of NK positive (NK+) cells and in slightly elevated NK cell activity. No alteration of NK cells, however, could be observed after presentation of the CS-. A second re-exposure of the CS+ on test trial 3, again resulted in a marked increase of NK+ cell number as well as in significantly elevated NK cell activity. The data presented here extend previous observations of conditioned alteration of immune responses in humans and indicate that the human organism might be able to react differentially to external stimuli, which have been associated with different immunological consequences.