VIP and PACAP inhibit IL-12 production in LPS-stimulated macrophages.: Subsequent effect on IFNγ synthesis by T cells

Since IL-12 plays a central role against intracellular pathogens, and contributes to the pathogenesis of immune diseases, its regulation is essential. This study examines the effect of two neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), on interleukin-12 (IL-12) production. VIP/PACAP inhibit IL-12 dose-dependently. Type I VIP receptor (VPAC1), and to a lesser degree type 2 VIP receptor (VPAC2), mediate the inhibition of IL-12, primarily through the cAMP/PKA pathway. VIP/PACAP inhibit the production of IL-12, IL-6, tumor necrosis factor cu (TNF alpha), and interferon gamma (IFN gamma) in vivo in endotoxemic mice. The presence of VIP/PACAP in the lymphoid organs and the specific effects on cytokine production offer a physiological basis for their immunomodulatory role in vivo. (C) 1999 Elsevier Science B.V. All rights reserved.