Gastrointestinal regulatory peptides modulate in vitro immune reactions of mouse lymphoid cells

The effects of six gastrointestinal regulatory peptides (beta-endorphin, substance P, metenkephalin, vasoactive intestinal peptide, bombesin, and somatostatin) on mouse lymphocytes stimulated with concanavalin A, lipopolysaccharide, phytohemagglutinin, or alloantigens were evaluated. Lymphocytes were stimulated in vitro and the influences of exogenously adding varying concentrations of neuropeptides (10(-6)-10(-11) M) on the incorporation of [methyl-3H-]thymidine were determined. The roles of cell density and antigen concentration on neuropeptide induced immunomodulation were also assessed. We observed that vasoactive intestinal peptide (VIP) would significantly inhibit the response of B10 lymphocytes to concanavalin A (54%) and phytohemagglutinin (56%) but not to lipopolysaccharide (16%). The VIP-induced inhibition was progressively diminished as the neuropeptide concentration was reduced to 10(-11) M. By 24 hr after stimulation the lymph node cells were refractory to the inhibitory effects of VIP. In addition, VIP would not inhibit B10 lymph node cells from responding to B10. K spleen cells in mixed, one-way lymphocyte cultures. The other five peptides did not influence the in vitro responses. The potential role of neuropeptides in the pathophysiology of immunologic-based disorders is discussed.