Figure 1. Effects of VIP and PACAP on activated macrophages. VIP or PACAP released in the vicinity of activated macrophages bind to specific receptors (VPAC1, VPAC2, PAC1) and inhibit expression and production of pro-inflammatory agents (TNF
, IL-6, nitric oxide [NO], chemokines [CK], and IL-12) and, indirectly, through IL-12, VIP, and PACAP inhibit IFN
production from antigen-stimulated Th cells. In contrast, VIP and PACAP up-regulate the production of IL-10, an anti-inflammatory cytokine. VIP and PACAP also inhibit expression of the co-stimulatory molecules B7.1 and B7.2, and the subsequent induction of T-cell proliferation. The in vivo inhibitory effects on pro-inflammatory cytokines and the up-regulation of the anti-inflammatory cytokine IL-10 correlate with the protective effects of VIP and PACAP against septic shock (Delgado et al., 1999f) and in experimental arthritis (Delgado et al., 2001). Macrophage-derived molecules inhibited by VIP/PACAP are boxed in shaded areas, whereas those up-regulated by VIP/PACAP are boxed in clear areas.
