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

Since IL-12 plays a central role against intracellular pathogens, and contr ibutes 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 (PACA P), on interleukin-12 (IL-12) production. VIP/PACAP inhibit IL-12 dose-depe ndently. Type I VIP receptor (VPAC1), and to a lesser degree type 2 VIP rec eptor (VPAC2), mediate the inhibition of IL-12, primarily through the cAMP/ PKA pathway. VIP/PACAP inhibit the production of IL-12, IL-6, tumor necrosi s factor cu (TNF alpha), and interferon gamma (IFN gamma) in vivo in endoto xemic mice. The presence of VIP/PACAP in the lymphoid organs and the specif ic effects on cytokine production offer a physiological basis for their imm unomodulatory role in vivo. (C) 1999 Elsevier Science B.V. All rights reser ved.