In the past few years, a large body of work has been published implicating a specific bidirectional communication between the neuroendocrine system and the immune system. Neuropeptides are biosynthesized by immune cells and immune factors with biological activity are biosynthesized by nerve cells. Furthermore, neuropeptides and in particular opiate peptides are known to activate lymphocytes to secrete Interleukins, and Interleukins have been found to specifically modulate the biosynthesis and release of peptide hormones by the cells of the neuroendocrine system. The focus of research in this laboratory is: (A) on the ability of normal and activated lymphoid cells to biosynthesize, process and secrete Proopiomelanocortin (POMC) related peptides; (B) on the modulation of POMC expression in lymphoid cells by neural signals; and (C) on the modulation of POMC expression in neuroendocrine cells by known immune factors. Experiments in this area of research have provided good evidence for neuroimmune signaling that leads to physiologically relevant hormonal responses. Dr. Zakarian has demonstrated for the first time, that the regions of the pituitary can be modulated by T cell dependent and T cell independent immune mechanisms giving rise to contrasting B-endorphin processing patterns in each region. Thus transplantation immunity seems to modulate B-endorphin activation in the pars intermedia while Interleukin-1 modulates the activation and release of B-endorphin and ACTH from the anterior pituitary. With these studies, an understanding may be gained of the coordinate activation of multiple signals, "neuro or immuno", that may be essential for the generation of biologically active peptide hormones in the immune system and in the neuroendocrine system.