Our paper belongs to the neuroimmunomodulation area of research which studies the basic framework constituted by the three systems involved in homeostasis: the nervous, the endocrine, and the immune systems. Over the last decades, neuroimmunomodulation has emerged as an integrative science in the borderland area between neuroscience, endocrinology, and immunology. An important factor for the behavior of this circuit is the presence of common mediators. The fact that the nervous and endocrine systems produce similar mediators was soon established, and it was only later on when the immune system was also found to be involved. In this sense, our paper represents a different approach to the study of Vasoactive Intestinal Peptide (VIP), a traditional nervous and endocrine factor. On the other hand, it also could be the consideration of the new idea that an endogenous peptide could be used as a potential therapeutic agent for the treatment of inflammatory and autoimmune diseases.

Originally, in 1969, Said and Mutt reported to the scientific community for the first time the presence in the lung of a 28-aminoacid peptide that was later isolated from the small intestine and then described in an article published with the premonitory title of "Polypeptide with broad biological activity: isolation from small intestine." It was later also isolated in the central and peripheral nervous system, acting as a neurotransmitter, and it is today being "rediscovered" by our group as an important immunomodulator. In this sense, our group has contributed to this "VIP rediscovery" demonstrating not only the immune source of VIP but also its important role in innate and adaptative immunity, expanding the research to the point where prospective clinical research could now be a reality.

Since 1980, when Blalock and Smith demonstrated that immune cells could produce both ACTH and endorphins and when, in spite of years of reticence about examining the endogenous production of neuroendocrine mediators by cells of the immune system, it has now become clearly established that the nervous, endocrine, and immune systems speak a common biochemical language—sharing both ligands and receptors. Although the important functional role played by these common mediators in the immune system is well accepted by the scientific community, a fact that should not be ignored is that their source is not only the innervation of the lymphoid organs but also the immune cellular origin. We described VIP as a "Very Important Peptide" for the first time in 1996 in a monograph volume of the unfortunately extinct journal Advances in Neuroimmunology—where I participated as Guest Editor. In our January 2001 paper in the journal Current Pharmaceutical Design, we have considered certain basic aspects of VIP and their receptors in the immune cells which have opened the way to suggest potential therapeutic roles for this peptide; we also have cited some of the strongest examples that actually support an important role of this peptide in the treatment of inflammatory and autoimmune diseases. In this sense, our review has represented a key that has opened the door for the knowledge of VIP as a curative agent while also showing up in some pathologies as septic shock (PNAS, 99:1053-1058, 2002), Rheumatoid arthritis (Nature Medicine,7:563-568, 2001) and Crohn’s disease (Gastroenterology, 124:961-971, 2003).

In 1989, in testing a battery of antibodies against neuropeptides in different lymphoid organs by means of immunohistochemistry, we showed VIP immunoreactivity in thymus, spleen, and lymphoid nodes. Since this year, our group continues, with great enthusiasm, in-depth studies on the future use of this "immunopeptide" as a beneficial drug.