VASOACTIVE-INTESTINAL-PEPTIDE AND PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE-38 INHIBIT IL-10 PRODUCTION IN MURINE T-LYMPHOCYTES

Vasoactive intestinal peptide (VIP), a neuropeptide present in the pep tidergic innervation of lymphoid organs and expressed in thymocytes an d peripheral lymphocytes has been previously reported to modulate cyto kine expression in T lymphocytes. In this study, we investigated the e ffects of VIP and of the structurally related neuropeptide PACAP-38 on the expression of IL-10 in murine lymphocyte cultures, Both neuropept ides inhibit IL-10 production by spleen cells or thymocytes activated via the TCR-associated CD3 complex in a similar dose-response manner, The inhibition is specific, presumably mediated through the VIP-R1, an d maximum inhibitory levels are achieved within the first 5 to 15 min of exposure to VIP or PACAP-38. CD4(+) T cells Function as direct cell ular targets for the two neuropeptides. The fact that VIP, PACAP-38, a nd forskolin, all known cAMP inducers, also inhibit IL-10 production, suggests the participation of cAMP in signal transduction, VIP and PAC AP-38 regulate transcriptional expression of IL-10, since IL-10 steady state mRNA levels are significantly reduced by treatment with the two neuropeptides. These results expand the range of neuroendocrine-regul ated cytokines and support the idea that neuropeptides such as VIP and PACAP, which are released or produced in the local lymphoid microenvi ronment and specifically modulate the expression of various cytokines, may participate in the intricate cytokine network controlling local i mmune responses.