Interleukin-10 (IL-10) is a recently discovered cytokine having a broad range of activities in the immune system including modulation of interferon-and antibody responses. The neuropeptide ACTH has similar activities. In addition, both are induced by Epstein-Barr virus in B- lymphocytes. Considering these similarities and the accumulating evidence supporting communication between the immune and neuroendocrine systems, it would be important to determine what roles IL-10 plays in this interaction. Supporting this, our preliminary evidence strongly indicates that IL-10 is produced by the pituitary and hypothalamus and, in addition, induces the production of corticotropin (ACTH) in pituitary cells and lymphocytes. The overall objective of this proposal is to determine the roles of IL-10 in the interaction/regulation of the immune and neuroendocrine axis. Specifically, we plan to determine: 1. the effects of IL-10 on the production and action of hormones in cells of neuroendocrine origin; 2. the effects of IL-10 on the production and action of hormones in lymphocytes; 3. the effects of viral IL-10 in a fashion similar to aims 1 & 2; 4. the expression of both IL-10 and its receptor in mouse, rat, and human neuroendocrine tissues; 5. the effects of IL-10 on Stat 1 p91 and p84 transcription factors in neuroendocrine cells; 6. the effects of IL-10 on hormonal responses in vivo utilizing a mouse model. These studies will provide information on this broadly active and important cytokine and its role in regulation of the immune and neuroendocrine axis during normal homeostasis and in abnormal states, such as endocrine and immune dysfunction and infectious process, i.e., AIDS.