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) a nd immune system are demonstrated by the modification of immune functi on 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 gustator y conditioned stimulus. The conditioned effects were compared to contr ol 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 i n the spleen is significantly suppressed, and the survival time of het erotopic heart allografts prolonged. These effects are paralleled by c onditioned 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 proliferatio n and cytokine production is completely abrogated after surgical dener vation of the spleen. Thus, during conditioning, the CNS learns to rei nstate at demand a CsA-like immunosuppression via splenic innervation. This might be used as a supportive therapy for controlling immune fun ctions. (C) 1998 Elsevier Science B.V. All rights reserved.