VIP and PACAP inhibit IL-12 production in LPS-stimulated macrophages. Subsequent effect on IFNgamma 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 1 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 alpha (TNFalpha), and interferon gamma (IFNgamma) 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.
Delgado
M
M
Department of Biological Sciences, Rutgers University, Newark, NJ 07102-1811, USA. dganea@andromeda.rutgers.edu
Munoz-Elias
E J
EJ
Gomariz
R P
RP
Ganea
D
D
D000818:Animals; D019446:Endotoxemia / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics; D018005:Receptors, Vasoactive Intestinal Peptide / Q000502:physiology; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; D008070:Lipopolysaccharides; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C495507:Vipr1 protein, mouse; C495510:Vipr2 protein, mouse; D016753:Interleukin-10; D018664:Interleukin-12; D014660:Vasoactive Intestinal Peptide; D007371:Interferon-gamma