Changes with age in the modulation of natural killer activity of murine leukocytes by gastrin-releasing peptide, neuropeptide Y and sulfated cholecystokinin octapeptide

Several investigations have suggested that the interactions between the nervous and immune systems are modified with age. The aim of the present work was to study the effect of three neuropeptides: gastrin-releasing peptide (GRP), neuropeptide Y (NPY) and sulfated cholecystokinin octapeptide (CCK-8 s) on natural killer (NK) activity of spleen, thymus and axillary node leukocytes from BALB/c male, young (8 ± 1 weeks), adult (24 ± 2 weeks) and old (72 ± 2 weeks) mice. We used cells from murine lymphoma YAC-1 as targets for the cytotoxic assay and three physiological concentrations of the neuropeptides (10⁻⁸, 10⁻¹⁰ and 10⁻¹² M). In control samples, in the absence of neuropeptide, we observed a decreased NK activity in young and old mice with respect to the adults in the three organs studied. Regarding the effect of the neuropeptides, GRP stimulates the cytotoxic activity of leukocytes from all locations, in adult animals. At the same age, NPY also stimulates the NK activity of leukocytes from axillary nodes and thymus, whereas it decreases the NK activity of spleen leukocytes from young mice. CCK-8 s has an inhibitory effect on the axillary node leukocytes from young mice and spleen leukocytes from old animals. However, CCK-8 s increased the NK activity of thymus leukocytes from young and adult mice. The results indicate that the highest values of NK activity are found in adult mice, and that the stimulating effect of the three neuropeptides studied on NK activity of leukocytes from adult mice are reduced or disappeared, in general, in old as well as in young animals. Furthermore, the changes observed with ageing in the modulation of NK activity by the neuropeptides studied suggest an altered integration of the nervous and immune systems.