Behaviorally conditioned immunosuppression using cyclosporine A: central nervous system reduces IL-2 production via splenic innervation.

Bi-directional interactions between the central nervous system (CNS) and immune system are demonstrated by the modification of immune function using behavioral conditioning. However, the mechanisms by which the CNS achieves conditioned immunomodulation are still in question. Here, we report that the immunosuppressive effects of cyclosporine A (CsA) can be behaviorally conditioned in rats using saccharin as a gustatory conditioned stimulus. The conditioned effects were compared to control groups that received CsA paired with water (sham-conditioned), CsA injection on test days (CsA-treated), and unhandled rats (untreated). In conditioned animals, the mitogen-induced lymphocyte proliferation in the spleen is significantly suppressed, and the survival time of heterotopic heart allografts prolonged. These effects are paralleled by conditioned inhibition of IL-2 and IFN-gamma synthesis by splenocytes. Furthermore, the CNS-induced immunosuppression is mediated neuronally and not via the blood, since the conditioned reduction of proliferation and cytokine production is completely abrogated after surgical denervation of the spleen. Thus, during conditioning, the CNS learns to reinstate at demand a CsA-like immunosuppression via splenic innervation. This might be used as a supportive therapy for controlling immune functions.