Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock.
Vasoactive intestinal peptide (VIP) is a neuropeptide that can modulate several immune aspects. Previous reports showed that VIP attenuates the deleterious consequences of septic shock by inhibiting the production of pro-inflammatory agents and stimulating the production of anti-inflammatory cytokines in activated macrophages. In this study, by using selective VIP agonists, we investigated the differential involvement of the VIP receptors in the anti-inflammatory role of VIP. Both the type 1 VIP receptor (VPAC1) agonist, [K(15), R(16), L(27)] VIP 1-7-GRF 8-27, and the type 2 VIP receptor (VPAC2) agonist, Ro25-1553, protected mice from lethal endotoxemia by inhibiting the macrophage-derived pro-inflammatory mediators IL-6, TNF-alpha, IL-12 and NO, and by stimulating the production of the anti-inflammatory cytokine IL-10. In addition, both VIP and VPAC1 agonist, but not the VPAC2 agonist, reduced in vitro and in vivo the expression of the co-stimulatory B7. 1/B7.2 molecules, and the subsequent stimulatory activity for T helper cells in stimulated macrophages. The higher effectiveness of the VPAC1 agonist compared with the VPAC2 agonist suggests that VPAC1 is the major mediator of the anti-inflammatory action of VIP. Since VIP and the two agonists appear to affect multiple cytokines and inflammatory factors, they might provide a more efficient therapeutical alternative to the use of specific cytokine antibodies or antagonists.
Delgado
M
M
Departamento de Biologia Celular, Facultad de Biologia, Universidad Complutense, Madrid, Spain.
Gomariz
R P
RP
Martinez
C
C
Abad
C
C
Leceta
J
J
D000818:Animals; D005260:Female; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D018005:Receptors, Vasoactive Intestinal Peptide / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology
D008070:Lipopolysaccharides; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide