Neuroendocrine regulation of mucosal immunity

In view of the extensive innervation of the gastrointestinal tract, including the mucosa, and the high number of immune effector cells present in this tissue, we have studied the effects of certain neurotransmitters on immune responses. We have concentrated on the effects of the neuropeptides substance P (SP), somatostatin (SOM) and vasoactive intestinal peptide (VIP). We have found that SP causes an increase in the proliferation of Peyer's patch lymphocytes as well as immunoglobulin (especially IgA) synthesis, when compared to splenic cells; and that there is a greater expression of SP receptors on lymphocytes derived from Peyer's patches compared to the spleen, without a significant difference in the expression between subsets of T and B cells. Furthermore, we have shown that intraepithelial leukocytes (IEL) show significantly increased cytotoxic activity following incubation with SP; whereas splenic lymphocytes were not stimulated in the same system. The effects of SOM where bi-directional depending upon the concentration employed but in general, SOM was inhibitory, in terms of proliferation, as was VIP. Although many more experiments are required to prove a physiological significance for the results that we have obtained, and to examine the whole gamut of neurotransmitters, we suggest that neuroendocrine regulation may play an important part in mucosal immunity.