The role of the autonomous nervous system in the dialogue between the brain and immune system

The concept of an extrinsic regulation of the immune system through neuroendocrine signals is well established, as is the fact that the immune system in turn informs the brain about contacts with antigens via “immunotransmitters”, i.e. cytokines and/or hormones with central effects [1]. All these data that have accumulated during the last twenty years have contributed to the vision of the immune system as “the sixth sense” [2]. While there is certainly still more work needed to define the physiology of this concept in all details, strong evidence has been obtained that the immune-neuroendocrine dialogue is of relevance for the homeostasis of the immune response, as defects in the activation of the hypothalamo-pituitary-adrenal (HPA) axis by immune signals were found to be associated with and/or to predispose to spontaneously occurring [3] and experimentally induced autoimmune diseases in animal models [4, 5], and there is evidence that the same is true also in humans [6]. A large body of more recent literature data strongly suggests that this dialogue involves not only the hypothalamus, but several other brain areas, notably the structures of the “Limbic System” (for review see [7]).