Vasoactive intestinal peptide synergizes with TNF-alpha in inducing human dendritic cell maturation

We investigated the effects of different neuropeptides on human dendritic c ells (DC) maturation. Immature DC, derived from monocytes cultured for 6 da ys with IL-4 plus GM-CSP, have been exposed to somatostatin, substance P, o r vasoactive intestinal peptide (VIP), Among these neuropeptides, only VIP induces the production of bioactive IL-12 and the neoexpression of CD83 on a fraction of the DC population, with an effect significant at 100 and 10 n M, respectively. These effects of VIP are dose-dependent, unaffected by pol ymixin B, and partly prevented by a VIP receptor antagonist. Although the e ffects of VIP alone remain modest, it synergizes with TNF-alpha to induce D C maturation. In the presence of a suboptimal concentration of TNF-alpha, w hich has no detectable effect on DC by itself, VIP induces the production o f high levels of bioactive IL-12, the neoexpression of CD83 on almost all t he DC population (with an effect significant at 10 and 0.1 nM, respectively ), and the up-regulation of various adhesion and costimulatory molecule exp ression. Moreover, DC exposed to VIP plus a suboptimal concentration of TNF -alpha are as potent as mature DC obtained by treatment with an optimal con centration of TNF-alpha in stimulating allogenic T cell proliferation, Our data suggest that, in inflammatory sites, VIP may cooperate with proinflamm atory mediators, such as TNF-alpha, to induce DC maturation.