ABSTRACT

The nervous system regulates the immune system through the innervation of lymphoid organs, in which the released neurotransmitters reach the immune cells. From the great number of neurotransmitters, some have been studied in relation to their possible action on immune response, neuropeptides being the least known as regards their immunomodulation capacity. Thus, the effects of several neuropeptides such as vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), neuropeptide Y (NPY) and cholecystokinin (CCK) on immune response are still relatively unknown. VIP is the most extensively investigated by different research groups, while other neuropeptides have been scarcely studied. Their effects may occasionally differ depending on the immune cell and function studied, and therefore, one should not expect to find compounds with a consistent immunosupressor or immunostimulant effect. Moreover, the action of neuropeptides may not be directly exerted on all kinds of immune cells, being possibly mediated by other cell types. The above may be due to the different kinds of neuropeptides receptors found on immune cells, the different intracellular pathways of signals or the presence of different environments for the cells studied. Thus, VIP inhibits (probably because of cAMP mediation) the lymphocyte functions, while it stimulates the phagocytic activity in macrophages (increasing the intracellular protein kinase C, PKC, activity). On the other hand, other neuropeptides such as CCK inhibit both lymphocyte and phagocyte functions through an increase in intracellular levels of cAMP, whereas NPY, GRP and bombesin-related peptides stimulate several functions of lymphocytes, macrophages and NK cells through PKC stimulation, with exceptions depending on the location of cells. In all cases, the effects observed occurred at physiological concentrations of the neuropeptides  (10^-9, 10^-10 or 10^-11 M) among the extensive range of concentrations used (from 10^-6 to 10^-14 M). All these data support the idea that neuropeptides constitute a complicated net of modulators of immune function which act directly or through the production of other mediators.