Conversation galante: how the immune and the neuroendocrine systems talk to each other.

The generation of endogenous adjuvants and the clearance of apoptotic cells occur at the intersection between the neuroendocrine and the immune systems. Recent data suggest that autoimmunity associates with a communication breakdown between the two systems and that events taking place in lymphoid organs and in peripheral inflamed tissues shape the response to tissue damage. Autonomic nerve endings release norepinephrine and acetylcholine, whereas sensitive fibers release neuropeptides. Moreover, nervous endings in the tissues control the secretory activity of neuroendocrine cells, which are distributed in the gut, the pancreas, the lung, the thyroid, the liver, the prostate, the skin. Intracellular enzymes, and in particular the 11 beta-hydroxysteroid dehydrogenase type 1, regulate the availability of active glucocorticoids in inflammatory macrophages and maturing dendritic cells; in turn the rate of active glucocorticoids determine the efficiency of phagocytes in clearing apoptotic cells, possibly influencing the availability of autoantigens. Immune cells release cytokines, which, in turn signal to the central and peripheral nervous system. We learnt from cytokine-neutralizing therapies that the sustained production of pro-inflammatory signals interferes with various neuro-endocrine axes. A better molecular dissection of this finely regulated inter-system cross-talk, in physiological conditions and during self-sustaining inflammatory diseases, might enable more rational therapeutic approaches.