Neuropeptides as signal molecules in common with leukocytes and the hypothalamic-pituitary-adrenal axis

There exists a bidirectional regulatory circuit between the nervous and immune systems. This regulation has been shown to be mediated in part through neuroendocrine hormones and cytokines. Both systems have receptors for both types of signal molecules. The nervous system has receptors for cytokines and it also synthesizes cytokines. The immune system synthesizes and responds to cytokines. So, it is not too far-fetched to believe that neuroendocrine peptide hormones could bind to leukocytes and modulate immune functions. However, it is not widely known that the immune system also synthesizes functional, neuropeptide hormones. This will be discussed in this paper citing a plethora of evidence. The aim of this paper is to summarize this evidence by using three neuropeptides that are synthesized by leukocytes and modulate immune functions as examples; corticotropin (ACTH), endorphin (END), and corticotropin releasing factor (CRF). The production and action of these three neuropeptides in the immune system will be explained. Finally, the potential physiological role of leukocyte-derived ACTH, END, and CRF in inflammation as a localized hypothalamic-pituitary-like axis is discussed.