CNS–immune system interactions: Conditioning phenomena

Abstract Converging data from different disciplines indicate that central nervous system processes are capable of influencing immune responses. This paper concentrates on recent studies documenting behaviorally conditioned suppression and enhancement of immunity. Exposing rats or mice to a conditioned stimulus previously paired with an immunomodulating agent results in alterations in humoral and cell-mediated immune responses to antigenic stimuli, and unreinforced reexposures to the conditioned stimuli result in extinction of the conditioned response. Although the magnitude of such conditioning effects has not been large, the phenomenon has been independently verified under a variety of experimental conditions. The biological impact of conditioned alterations in immune function is illustrated by studies in which conditioning operations were applied in the pharmacotherapy of autoimmune disease in New Zealand mice. In conditioned animals, substituting conditioned stimuli for active drugs delays the onset of autoimmune disease relative to nonconditioned animals using a dose of immunosuppressive drug that, by itself, is ineffective in modifying the progression of disease. The hypothesis that such conditioning effects are mediated by elevations in adrenocortical steroid levels receives no support from available data. Despite its capacity for self-regulation, it appears that the immune system is integrated with other psychophysiological processes and subject to modulation by the brain.