Hormone regulation of immune homeostasis: local or long distance?

The endocrine system and the immune system consist of dynamic biological processes involved on the one hand in the regulation of a complex array of metabolic and physiologic activities, and on the other hand in protection against infection and disease. Evidence for bidirectional functional involvement of immune-endocrine interactions can be seen at many levels, including codependence during critical stages of development, the complementary use of shared molecular mediators and receptors by both systems, and the integrated participation of the immune system and the endocrine system in resistance or susceptibility to disease. Moreover, recent findings-principally derived from studies of intestinal intraepithelial lymphocytes in mice--suggest that immune-endocrine interactions are essential for the proper development of intestinal T cells, and indicate that this most likely occurs via a local network of hormone synthesis and utilization. In the present article, these findings will be discussed in the context of immune-endocrine collaboration, with particular attention given to the involvement of the thymus in this process, and a hypothesis will be proposed which suggests that the homeostatic balance between health and disease is largely driven by local rather than systemic hormonal regulatory events.